Diaminopyrimidine derivatives and processes for the preparation thereof

ABSTRACT

The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT4 receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.

CROSS-REFERENCE TO PRIOR APPLICATIONS

This is a Divisional Application of U.S. patent application Ser. No. 14/001,489, filed on Aug. 23, 2013, which was a National Phase Application filed under 35 U.S.C. § 371 as a national stage of PCT/KR2012/001427, filed on Feb. 24, 2012, an application claiming the benefit under 35 U.S.C. § 119 of the Korean Application No. 10-2011-0016981, filed on Feb. 25, 2011 the content of each of which is hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a novel 5-HT₄ receptor agonist, more specifically a novel diaminopyrimidine derivative or its pharmaceutically acceptable salt having an activity as a 5-HT₄ receptor agonist, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof.

BACKGROUND ART

Serotonin (5-hydroxytryptamine, 5-HT), one of the neurotransmitters, is broadly distributed throughout human body including both the central nervous system and the peripheral nervous system. Approximately 95% of the human body's total serotonin is found in the gastrointestinal tract, while about 5% thereof is found in the brain. Serotonin receptors are located in intestinal nerves, enterochromaffin cells, intestinal smooth muscle, immune tissues, etc. Serotonin receptor subtypes include 5-HT₁, 5-HT₂, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, and 5-HT₇. Interactions between these various receptors and serotonin are linked to various physiological functions. Therefore, various researches have been performed for developing therapeutic agents that are capable of interacting with a specific serotonin subtype as a target. The researches include identification of 5-HT₄ receptors and active agents interacting therewith (Langlois and Fischmeister, J. Med. Chem. 2003, 46, 319-344).

It has been found by the previous literatures that 5-HT₄ receptor agonists are useful for treating an abnormal gastrointestinal motility, i.e., dysfunction in gastrointestinal motility. The abnormal gastrointestinal motility may result in various disorders, for example irritable bowel syndrome (IBS), constipation, dyspepsia, delayed gastric emptying, gastroesophageal reflux disease (GERD), gastroparesis, post-operative ileus, intestinal pseudo-obstruction, drug-induced delayed transit, etc.

Representative 5-HT₄ receptor agonists disclosed in prior arts include tegaserod (an aminoguanidine derivative, U.S. Pat. No. 5,510,353), prucalopride (a benzofuran carboxamide derivative, EP0445862), cisapride (a benzamide derivative, U.S. Pat. No. 4,962,115), mosapride (EP0243959), etc. These compounds are known as an agent stimulating gastrointestinal motility.

DETAILED DESCRIPTION OF THE INVENTION Technical Problem

The present inventors found that a certain diaminopyrimidine derivative functions as a 5-HT₄ receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility.

Therefore, the present invention provides the above diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof.

Technical Solution

According to an aspect of the present invention, there is provided a use of a diaminopyrimidine derivative or its pharmaceutically acceptable salt for the manufacture of a medicament for preventing or treating a dysfunction in gastrointestinal motility

According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a dysfunction in gastrointestinal motility comprising a diaminopyrimidine derivative or its pharmaceutically acceptable salt as an active ingredient.

According to still another aspect of the present invention, there is provided a diaminopyrimidine derivative or its pharmaceutically acceptable salt.

According to still another aspect of the present invention, there is provided a process for preparing the diaminopyrimidine derivative or its pharmaceutically acceptable salt.

Advantageous Effects

The compound of the present invention, i.e., the diaminopyrimidine derivative or its pharmaceutically acceptable salt, functions as a 5-HT₄ receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.

BEST MODE FOR CARRYING OUT THE INVENTION

As used herein, the term “alkyl” refers to a straight or branched aliphatic hydrocarbon radical. For example, C₁-C₆ alkyl means a straight or branched aliphatic hydrocarbon having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, and isopentyl.

The term “alkoxy or alkyloxy” refers to a radical formed by substituting the hydrogen atom of a hydroxyl group with an alkyl. For example, C₁-C₆ alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, and isopentyloxy.

The term “alkenyl” refers to a straight or branched aliphatic hydrocarbon radical having one or more double bond(s). For example, C₂-C₆ alkenyl includes ethenyl, propenyl, butenyl, pentenyl, and hexenyl.

The term “alkynyl” refers to a straight or branched aliphatic hydrocarbon radical having one or more triple bond(s). For example, C₂-C₆ alkynyl includes ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

The present invention provides a use of a compound of Formula 1 or its pharmaceutically acceptable salt for the manufacture of a medicament for preventing or treating a dysfunction in gastrointestinal motility:

wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-, 3-dionyl, dihydrobenzoimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

In the use for the manufacture of a medicament for preventing or treating a dysfunction in gastrointestinal motility according to the present invention, the dysfunction in gastrointestinal motility includes gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony. The constipation includes chronic constipation, chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), etc. And also, the dyspepsia includes functional dyspepsia.

In the use for the manufacture of a medicament for preventing or treating a dysfunction in gastrointestinal motility according to the present invention, the compound or its salt may be the compound of Formula 1 or its pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E,

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The present invention also provides a pharmaceutical composition for preventing or treating a dysfunction in gastrointestinal motility comprising a therapeutically effective amount of a compound of Formula 1 or its pharmaceutically acceptable salt; and a pharmaceutically acceptable carrier

wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl, dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

In the pharmaceutical composition according to the present invention, the dysfunction in gastrointestinal motility includes gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony. The constipation includes chronic constipation, chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), etc. And also, the dyspepsia includes functional dyspepsia.

In the pharmaceutical composition according to the present invention, the compound or its salt may be the compound of Formula 1 or its pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E,

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperadinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable carrier, such as diluents, disintegrants, sweeteners, lubricants, or flavoring agents. The pharmaceutical composition may be formulated to an oral dosage form such as tablets, capsules, powders, granules, suspensions, emulsions, or syrups; or a parenteral dosage form such as injection. The dosage form may be various forms, e.g., dosage forms for single administration or for multiple administrations.

The pharmaceutical composition of the present invention may comprise, for example, a diluent (e.g., lactose, corn starch, etc), a lubricant (e.g., magnesium stearate), an emulsifying agent, a suspending agent, a stabilizer, and/or an isotonic agent. If necessary, the composition further comprises sweeteners and/or flavoring agents.

The composition of the present invention may be administered orally or parenterally, including intravenous, intraperitoneal, subcutaneous, rectal and topical routes of administration. Therefore, the composition of the present invention may be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of tablets for oral administration, carriers such as lactose, corn starch, and lubricating agents, e.g. magnesium stearate, are conventionally used. In the case of capsules for oral administration, lactose and/or dried corn starch can be used as a diluent. When an aqueous suspension is required for oral administration, the active ingredient may be combined with emulsifying and/or suspending agents. If desired, certain sweetening and/or flavoring agents may be used. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous administration, the total concentration of solutes should be controlled in order to render the preparation isotonic. The composition of the present invention may be in the form of an aqueous solution containing pharmaceutically acceptable carriers, e.g., saline having a pH level of 7.4. The solutions may be introduced into a patient's intramuscular blood-stream by local bolus injection.

The compound of Formula 1 or its pharmaceutically acceptable salt may be administered in a therapeutically effective amount ranging from about 0.001 mg/kg to about 10 mg/kg per day to a subject patient. Of course, the dosage may be changed according to the patients age, weight, susceptibility, symptom, or activity of the compound.

The present invention also provides a method for treating a dysfunction in gastrointestinal motility, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony, in a patient, which comprises administering a therapeutically effective amount of the compound of Formula 1 or its pharmaceutically acceptable salt to the patient in need thereof. The constipation includes chronic constipation, chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), etc. And also, the dyspepsia includes functional dyspepsia.

The present invention also provides a compound of Formula 1 or its pharmaceutically acceptable salt:

wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-, 3-dionyl, dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

Preferably, the compound or its salt may be the compound of Formula 1 or its pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E.

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The compound of Formula 1 or its pharmaceutically acceptable salt may have substituents containing asymmetric carbon and therefore be in the form of racemic mixture (RS) or in forms of optical isomers, such as (R) or (S) isomer. The compound of Formula 1 or its pharmaceutically acceptable salt comprises both racemic mixture (RS) and optical isomers such as (R) or (S) isomer. And also, the compound of Formula 1 or its pharmaceutically acceptable salt may be in the form of cis- or trans-geometrical isomer, according to substituents having e.g., the double bond therein. The compound of Formula 1 or its pharmaceutically acceptable salt comprises both cis- and trans-geometrical isomers. And also, the compound of Formula 1 or its pharmaceutically acceptable salt may be in the form of one or more diastereomic isomer(s) or a mixture thereof. The compound of Formula 1 or its pharmaceutically acceptable salt comprises both diastereomic isomer(s) and a mixture thereof.

The compound of Formula 1 of the present invention may be in a pharmaceutically acceptable salt form. The salt may be an acid addition salt form, which includes e.g., salts derived from an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfonic acid, sulfamic acid, phosphoric acid, or nitric acid; and salts derived from an organic acid such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, citric acid, maleic acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, tartaric acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, benzenesulfonic acid, oxalic acid or trifluoroacetic acid. The salt may be prepared by reacting a compound of Formula 1 in the form of free base with a salt-forming inorganic or organic acid in stoichiometric amount or excessive amount, in a suitable solvent or a mixture of two or more solvents.

In the use, the pharmaceutical composition, the treatment method, and the compound according to the present invention, more preferable compounds include a compound (or its pharmaceutically acceptable salt) selected from the group consisting of:

-   N-(4-fluorophenyl)-4-propyl-6-(pyrrolidin-1-yl)pyrimidin-2-amine; -   (S)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ol; -   (R)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   {1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   N-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (S)—N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (R)—N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-carboxamide; -   N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (R)—N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   2,2,2-trifluoro-N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   4-[3-(dimethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   (S)—N-(4-fluorophenyl)-4-propyl-6-[2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)—N-(4-fluorophenyl)-4-{2-[(phenylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-amine; -   (S)—N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   (S)-tert-butyl     1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate; -   4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   4-[3-(diethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   (S)—N-(4-fluorophenyl)-4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide; -   (S)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ol; -   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-6-amine; -   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-5-amine; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine; -   (S)—N-(3-chlorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)—N-(4-fluoro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)—N-(4-chloro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-3-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine; -   (S)-7-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one; -   (S)—N-(5-chloro-2-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)—N-(3-chloro-4-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)—N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine; -   (S)-2-fluoro-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-2-amino-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine; -   (S)-tert-butyl     1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate; -   3-{4-[3-(diethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide; -   (S)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (R)-3-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-3-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (R)-tert-butyl     {1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methylcarbamate; -   (R)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-3-[4-(3-methoxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}butyramide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}cyclopentanecarboxamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-(piperidin-1-yl)propanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}benzamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-fluorobenzamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenylacetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(4-fluorophenyl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-phenoxypropanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-isobutoxypropanamide; -   (S)-2-(4-benzylpiperazin-1-yl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(piperidin-1-yl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-oxo-4-phenylbutanamide; -   (S)-2-(4-aminophenyl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-cyclopentylacetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-methoxyacetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-2-yl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-4-yl)acetamide; -   (S,E)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-phenylbut-3-enamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(thiophen-2-yl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}isobutyramide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl)}3,3,3-trifluoropropanamide; -   3-[4-(2-oxopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-3-{4-[3-(hexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclohexylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(benzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(phenethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(3-phenylpropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(3-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(4-hydroxybenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(4-ethylbenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(isopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(pentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   3-{4-[(3S)-3-(2-methylbutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(isobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(4-methoxybenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(4-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-(4-{3-[bis(cyclopropylmethyl)amino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-3-{4-propyl-6-[3-(pyridin-2-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-propyl-6-[3-(pyridin-3-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-propyl-6-[3-(pyridin-4-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(2-ethylbutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(neopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(2-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-(4-propyl-6-{3-[3-(trifluoromethyl)benzylamino]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile; -   (S)-3-(4-propyl-6-{3-[4-(trifluoromethyl)benzylamino]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile; -   (S)-4-({1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}methyl)phenylacetate; -   (S)-3-(4-{3-[4-(dimethylamino)benzylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-3-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-propyl-6-[3-(thiophen-2-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-propyl-6-[3-(thiophen-3-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(dibutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-(4-{3-bis[3-(methylthio)propyl]aminopyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-3-{4-[3-(butylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-(4-{3-[3-(methylthio)propylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)—N-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-6-amine; -   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}isopropane-2-sulfonamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-fluorobenzenesulfonamide; -   3-{4-[(3S)-3-(sec-butylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(pentan-3-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(2,6-dimethylheptan-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(4,4-dimethylpentan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(3-hydroxy-3-methylbutan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(heptan-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(n-hexan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(5-methylhexan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-tert-butyl     2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}ethylcarbamate; -   (S)-3-{4-[3-(I-benzylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(1-benzoylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(1-acetylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclooctylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(cyclopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-tert-butyl     3-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}azetidine-1-carboxylate; -   (S)-3-(4-{3-[2-(benzyloxy)ethylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}propionamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}pivalamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2,2-dimethylbutanamide; -   (S,E)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-methylbut-2-enamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}hexanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-phenylpropanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(1H-indol-3-yl)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxy-2-m     ethylpropanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-(4-methoxyphenyl)propanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-(4-hydroxyphenyl)propanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-oxopentanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide; -   (S)-2-benzyloxy-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenoxyacetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(dimethylamino)acetamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-(dimethylamino)propanamide; -   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-dimethylaminobutanamide; -   N—(S)-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-ethoxyacetamide; -   N—(S)-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(2-methoxyethoxy)acetamide; -   (S)-benzyl     2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-2-oxoethylcarbamate; -   (S)-tert-butyl     3-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-3-oxobutylcarbamate; -   (S)-tert-butyl     4-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamoyl}piperidine-1-carboxylate; -   (R)-2-methyl-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (R)-2-amino-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-2-methyl-5-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine; -   (S)—N¹-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}3-nitrobenzene-1,4-diamine; -   (R)-3-{4-[3-(aminomethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-2-fluoro-5-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-2-fluoro-5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile; -   N-(4-fluorophenyl)-4-methyl-6-(pyrrolidin-1-yl)pyrimidin-2-amine; -   (3R,5S)-1-[2-(4-fluorophenyl)-6-propylpyrimidin-4-yl]-5-(hydroxymethyl)pyrrolidin-3-ol; -   (S)-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (R)-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   {1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (R)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-6-amine; -   N-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine; -   (S)-methyl     1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidine-2-carboxylate; -   N-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-3-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-2-yl)methanol; -   (S)-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(1H-benzo[d]imidazol-5-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-5-ylamino]pyrimidin-4-yl}pyrrolidin-2-yl)methanol; -   (S)-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-2-yl)methanol; -   (S)-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(5-methoxy-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(4-fluor-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-2-yl)methanol; -   (S)-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-2-fluoro-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-2-amino-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-3-{4-[3-(aminoethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(piperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-[3-(1-butylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)—N-{1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-3-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (R)-3-[4-butyl-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-ylamino]benzonitrile; -   (S)-3-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-tert-butyl     1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamate; -   (S)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-5-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile; -   (R)-5-[4-butyl-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-ylamino]-2-methylbenzonitrile; -   (S)-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-tert-butyl     1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamate; -   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]benzonitrile; -   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile; -   (S)-3-{4-butyl-6-[3-(isopropylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-butyl-6-[3-(diethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-butyl-6-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-5-{4-butyl-6-[3-(isopropylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-5-{4-butyl-6-[3-(diethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-5-(4-butyl-6-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino)-2-methylbenzonitrile; -   (S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[2-(4-methyl-2-oxo-2H-chromen-7-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-benzyl     5-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamate; -   (S)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-3-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzamide; -   (S)-3-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-N-methylbenzamide; -   (S)—N-[1-(2-{[3-(aminomethyl)phenyl]amino}-6-propyl     pyrimidin-4-yl)pyrrolidin-3-yl]acetamide; -   (S)-3-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-4-chlorobenzamide; -   (S)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(4-aminophenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(4-chloro-3-hydroxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)-4-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-hydroxybenzoic     acid; -   (S)-5-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-hydroxybenzoic     acid; -   (S)—N-(1-{2-[(3-hydroxy-4-methyl     phenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(3-chloro-4-hydroxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(4-hydroxy-3-methyl     phenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(3-fluoro-4-hydroxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(3-hydroxy-4-methoxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(3-methoxy-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-[1-(2-{[4-methyl-3-(trifluoromethyl)phenyl]amino)-6-propylpyrimidin-4-yl}pyrrolidin-3-yl]acetamide; -   (S)—N-(1-{2-[(3,4-dimethylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[(3-fluoro-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[2-(3-amino-4-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide -   N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(5-methoxy-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   N-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   N-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-5-ylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   N-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-methyl-2-oxo-2H-chromen-7-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(4-amino-3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (R)—N-(4-chloro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (R)-4-(2-methylpyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-ylamine; -   (R)—N-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine; -   (R)-4-(2-methylpyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine; -   (R)-4-methyl-7-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2H-chromen-2-one; -   (R)—N-(3-chloro-4-methylphenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (R)-4-(2-methylpyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-ylamine; -   (R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (R)—N-(4-methyl-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (R)—N-[4-fluor-3-(trifluoromethyl)phenyl]-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamine; -   (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine; -   (R)-benzyl     2-methoxy-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]phenylcarbamate; -   (R)-2-fluoro-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine; -   (R)-1-{6-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]indolin-1-yl}ethanone; -   (R)—N-(5-chloro-2-methylphenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine; -   (R)-4-methoxy-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine; -   (R)-4-chloro-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine; -   (R)-4-fluoro-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine; -   (R)-4-methyl-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine; -   (S)-3-{4-[3-(2-hydroxyethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-methyl     benzene-1,4-diamine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-chloro-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine; -   (S)—N-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(5-chloro-2-methyl     phenyl)-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-chloro-4-methyl     phenyl)-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine; -   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile; -   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile; -   (S)-2-amino-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-benzyl     5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamate; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-[3,5-bis(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine; -   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3,5-dimethoxyphenyl)-6-propylpyrimidin-2-amine; -   (S)-3-amino-5-{[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile; -   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzenesulfonamide; -   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine; -   (S)-4-fluoro-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine; -   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-4-methylbenzene-1,3-diamine; -   (S)-4-methoxy-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine; -   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}indolin-6-amine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]4-methyl     benzene-1,3-diamine; -   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]4-fluorobenzene-1,3-diamine; -   (S)—N-(4-chloro-3-nitrophenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine; -   (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile; -   (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine; -   (S)—N-(5-chloro-2-methylphenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)—N-(3-chloro-4-methylphenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine; -   (S)—N¹-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-4-methylbenzene-1,3-diamine; -   (S)—N¹-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine; -   3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)—N-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-4-ethyl-N-(4-fluorophenyl)-6-(2-methoxymethylpyrrolidin-1-yl)pyrimidin-2-amine; -   4-ethyl-N-(4-fluorophenyl)-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-amine; -   (S)-4-ethyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)pyrimidin-2-amine; -   (S)-3-[4-(3-phenoxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-2-amino-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol; -   (S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile; -   (S)-3-(4-{2-[(methylamino)methyl]pyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-3-(4-{2-[(cyclobutylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-3-(4-{2-[(4-fluorobenzylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-3-(4-propyl-6-{2-[(propylamino)methyl]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile; -   (S)-3-(4-{2-[(2-hydroxyethylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-2-methyl-5-{4-propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-2-methyl-5-(4-{3-[3-(methylthio)propylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile; -   (S)-5-{4-[3-(4-hydroxybenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile; -   (S)-5-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-5-(4-[3-(cyclobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-5-{4-[3-(cyclopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-5-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)-2-methyl-5-{4-[3-(pentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-2-methyl-5-{4-[3-(neopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile; -   (S)-5-(4-{3-[(4,5-dimethylfuran-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}propionamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenylacetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(piperidin-1-yl)acetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)     acetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-4-yl)acetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-(thiophen-2-yl)acetamide; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamide; -   (S)-1-(1-{2-[(3-cyano-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-3-ethylurea; -   (R)-3-(4-{3-[(diethylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile; -   (S)—N-{1-[6-butyl-2-(4-methyl-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[6-butyl-2-(4-fluoro-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[6-butyl-2-(4-chloro-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-butylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-butylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-(1-{6-butyl-2-[4-fluoro-3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)—N-{1-[6-butyl-2-(3-cyano-4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide; -   (S)-2-amino-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-4-butyl-N-(4-methyl-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)-4-butyl-N-(4-fluor-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)-4-butyl-N-(4-chloro-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)-3-amino-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine; -   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine; -   (S)-4-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-fluorobenzonitrile; -   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine; -   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-chlorobenzene-1,3-diamine; -   (S)-2-amino-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-3-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile; -   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine; -   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine; -   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluoro-3-nitrophenyl)pyrimidin-2-amine; -   (S)-4-butyl-N-(4-chloro-3-nitrophenyl)-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-amine; -   (S)-3-amino-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile; -   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}5-(trifluoromethyl)benzene-1,3-diamine; -   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}3-(trifluoromethyl)benzene-1,4-diamine; -   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]pyrimidin-2-amine; -   (S)-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-fluorobenzonitrile; -   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine; -   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-chlorobenzene-1,3-diamine; -   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide; -   (S)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide; -   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide; -   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide; -   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide; -   (S)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide; -   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide; -   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide; -   (S)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide; -   (S)-2-hydroxy-N-(1-{2-[4-methyl-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide; -   (S)-4-fluoro-N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine; -   (S)-3-amino-5-({4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile; -   (S)-2-amino-5-({4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile; -   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine; -   (S)—N¹-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}3-(trifluoromethyl)benzene-1,4-diamine; -   (S)-2-amino-5-({4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile; -   (S)—N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine; -   (S)-4-[3-(ethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;     and -   (S)—N-(1-{2-[(3,4-diaminophenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide.

In the use, the pharmaceutical composition, the treatment method, and the compound according to the present invention, still more preferable compounds in terms of pharmacological activity include the compound (or its pharmaceutically acceptable salt) described in Table 2-1 to Table 2-3.

The present invention includes, within its scope, a process for preparing a compound of Formula 1 or its pharmaceutically acceptable salt, which comprises reacting a compound of Formula 2 with a compound of Formula 3 to obtain a compound of Formula 4; performing a methylation of the compound of Formula 4 to obtain a compound of Formula 5; reacting the compound of Formula 5 with R₁—NH₂ to obtain a compound of Formula 6; performing a halogenation of the compound of Formula 6 to obtain a compound of Formula 7; and reacting the compound of Formula 7 with a compound of Formula 8 to obtain a compound of Formula 1:

wherein, R₁, R₂, R₃, R₄, and R₅ are the same as defined in the above; and X is halogen.

The compounds of Formula 2 and 3 are commercially available. The reaction between the compound of Formula 2 and the compound of Formula 3 may be performed in the presence of a base and a solvent. The base may be potassium carbonate, sodium carbonate, etc and the solvent may be an aqueous solvent such as water. Typically, the reaction may be carried out under heating.

The methylation of the compound of Formula 4 may be carried out using a methylating agent such as iodomethane. The methylation may be performed in the presence of a base and a solvent. The base may be sodium hydroxide, potassium hydroxide, etc and the solvent may be an aqueous solvent such as water. Typically, the methylation may be carried out at room temperature or under heating.

The reaction between the compound of Formula 5 and R₁—NH₂ may be performed in the absence of a solvent or in the presence of a solvent such as diglyme. The reaction may be carried out at a temperature ranging from 140° C. to 180° C.

The halogenation of the compound of Formula 6 may be carried out using a halogenating agent such as phosphorus oxychloride. The halogenation may be performed preferably at a temperature of about 100° C. or higher. And also, for improving reaction rate and/or yield, the halogenation may be performed in the presence of N,N-dimethylaniline or N,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 7 and the compound of Formula 8 may be performed in the presence of an organic solvent, such as anhydrous tetrahydrofuran, alcohol, and 1,4-dioxane. Typically, the reaction may be carried out under heating. And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of a metallic catalyst (e.g., palladium), a ligand, and a base such as cesium carbonate, triethylamine and diisopropylethylamine; or performed under microwave ranging from 300 W to 600 W.

The compound of Formula 5 may be also prepared by reacting a compound of Formula 2 with a compound of Formula 9:

wherein, R₅ is the same as defined in the above.

The compound of Formula 9 is commercially available. The reaction between the compound of Formula 2 and the compound of Formula 9 may be performed in the presence of a base and a solvent. The base may be potassium carbonate, sodium carbonate, etc and the solvent may be an aqueous solvent such as water. Typically, the reaction may be carried out at room temperature or under heating.

The compound of Formula 6 may be also prepared by reacting a compound of Formula 2 with a compound of Formula 10:

wherein, R₁ and R₅ are the same as defined in the above.

The compound of Formula 10 may be easily prepared by using known methods, e.g., EP0560726. The reaction between the compound of Formula 2 and the compound of Formula 10 may be performed in the presence of a base and a solvent. The base may be sodium methoxide, sodium ethoxide, etc and the solvent may be an alcohol. Typically, the reaction may be carried out under heating.

The present invention also provides a process for preparing a compound of Formula 1 or its pharmaceutically acceptable salt, which comprises performing a halogenation of a compound of Formula 4 to obtain a compound of Formula 11; reacting the compound of Formula 11 with a compound of Formula 8 to obtain a compound of Formula 12; and reacting the compound of Formula 12 with R₁—NH₂ to obtain a compound of Formula 1:

wherein, R₁, R₂, R₃, R₄, and R₅ are the same as defined in the above; and X is halogen.

The halogenation of the compound of Formula 4 may be carried out using a halogenating agent such as phosphorus oxychloride. The halogenation may be performed preferably at a temperature of about 100° C. or higher. And also, for improving reaction rate and/or yield, the halogenation may be performed in the presence of N,N-dimethylaniline or N,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 11 and the compound of Formula 8 may be performed in the presence of an organic solvent, such as anhydrous tetrahydrofuran, alcohol, chloroform, and N,N-dimethylformamide. Typically, the reaction may be carried out at room temperature or under heating. And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of a base such as triethylamine and diisopropylethylamine.

The reaction between the compound of Formula 12 and R₁—NH₂ may be performed in the presence of a solvent such as alcohol, toluene, 1,4-dioxane, and N,N-dimethylformamide. The reaction may be carried out under heating. And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of a metallic catalyst (e.g., palladium), a ligand, and a base (e.g., cesium carbonate); or performed under microwave ranging from 300 W to 600 W.

The compound of Formula 11 may be also prepared by reacting a compound of Formula 5 with an acid to obtain a compound of Formula 13; and then performing a halogenation of the compound of Formula 13:

wherein, R₅ and X are the same as defined in the above.

The reaction between the compound of Formula 5 and the acid may be performed using an organic acid (e.g., acetic acid, etc) and an inorganic acid (e.g. hydrochloric acid, etc). The reaction may be performed in an aqueous solvent such as water. Typically, the reaction may be carried out under heating.

The halogenation of the compound of Formula 13 may be carried out using a halogenating agent such as phosphorus oxychloride. The halogenation may be performed preferably at a temperature of about 100° C. or higher. And also, for improving reaction rate and/or yield, the halogenation may be performed in the presence of N,N-dimethylaniline or N,N-dimethylformamide in a catalytic amount.

In accordance with an embodiment of the present invention, there is provided a process for preparing a compound of Formula 1b or its pharmaceutically acceptable salt, which comprises reacting a compound of Formula 1a with an organic acid or an acyl halide:

wherein, R₁, R₂, R₄, R₅, R₆, and R₇ are the same as defined in the above.

The reaction between the compound of Formula 1a and the organic acid may be performed through amide coupling reaction, using a coupling agent such as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such as diisopropylethylamine and triethylamine. The coupling reaction may be performed in an organic solvent such as dichloromethane, and N,N-dimethylformamide. Typically, the coupling reaction is performed at room temperature.

And also, the reaction between the compound of Formula 1a and the acyl halide may be performed through amide coupling reaction, using an organic base (e.g., diisopropylethylamine, triethylamine, etc) or an inorganic base (e.g., sodium hydroxide, etc). The coupling reaction may be performed in an organic solvent such as dichloromethane or a mixed solvent of an organic solvent and water. Typically, the coupling reaction is performed at room temperature.

The compound of Formula 1b or its pharmaceutically acceptable salt may be also prepared by reacting a compound of Formula 12a with an organic acid or an acyl halide to obtain a compound of Formula 12b; and then reacting the compound of Formula 12b with R₁—NH₂ to obtain a compound of Formula 1b:

wherein, R₁, R₂, R₄, R₅, R₆, and R₇ are the same as defined in the above; and X is halogen.

The reaction between the compound of Formula 12a and the organic acid may be performed through amide coupling reaction, using a coupling agent such as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such as diisopropylethylamine or triethylamine. The coupling reaction may be performed in an organic solvent such as dichloromethane, and N,N-dimethylformamide. Typically, the coupling reaction is performed at room temperature.

And also, the reaction between the compound of Formula 12a and the acyl halide may be performed through amide coupling reaction, using an organic base (e.g., diisopropylethylamine, triethylamine, etc) or an inorganic base (e.g., sodium hydroxide, etc). The coupling reaction may be performed in an organic solvent such as dichloromethane or a mixed solvent of an organic solvent and water. Typically, the coupling reaction is performed at room temperature.

The reaction between the compound of Formula 12b and R₁—NH₂ may be performed in an organic solvent such as alcohol, toluene, 1,4-dioxane, and N,N-dimethylformamide, etc. Typically, the reaction may be performed under heating. And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of a metallic catalyst (e.g., palladium), a ligand, and a base (e.g., cesium carbonate); or performed under microwave ranging from 300 W to 600 W.

In accordance with another embodiment of the present invention, there is provided a process for preparing a compound of Formula 1c or its pharmaceutically acceptable salt, which comprises performing a reductive amination using an aldehyde or a ketone with respect to a compound of Formula 1a:

wherein, R₁, R₂, R₄, R₅, R₈, and R₉ are the same as defined in the above.

The reductive amination may be performed using a reducing agent such as sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride. The reductive amination may be performed in an organic solvent (e.g., alcohol) at room temperature or at low temperature (e.g., at 0° C. or less). And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of acetic acid, etc.

The compound of Formula 1c or its pharmaceutically acceptable salt may be prepared by introducing an amine-protecting group to a compound of Formula 12a to obtain a compound of Formula 12c; performing an alkylation of the compound of Formula 12c to obtain a compound of Formula 12d; and reacting a compound of Formula 12d with R₁—NH₂, followed by removing the amine-protecting group:

wherein, R₁, R₂, R₄, R₅, and R₈ are the same as defined in the above; X is halogen; and R₉ is hydrogen. P is an amine-protecting group such as tert-butoxycarbonyl.

The reaction for introducing an amine-protecting group to the compound of Formula 12a may be performed in an organic solvent such as dichloromethane, chloroform, and 1,4-dioxane at room temperature or at low temperature (e.g., at 0° C. or less). And also, the reaction may be performed in the presence of a base such as triethylamine, diisopropylethylamine, and 4-dimethylaminopyridine.

The alkylation of the compound of Formula 12c may be performed using an alkyl halide. The alkylation may be performed in the presence of a base (e.g., sodium hydride) in an organic solvent (e.g., N,N-dimethylformamide). The alkylation may be performed at room temperature or under heating.

The reaction between the compounds of Formula 12d and R₁—NH₂ may be performed in an organic solvent such as alcohol, toluene, 1,4-dioxane, and N,N-dimethylformamide. Typically, the reaction is performed under heating. And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of a metallic catalyst (e.g., palladium), a ligand, and a base (e.g., cesium carbonate); or performed under microwave ranging from 300 W to 600 W. The reaction for removing the amine-protecting group may be performed using an acid (e.g., hydrochloric acid, trifluoroacetic acid, etc) in an organic solvent such as ethyl acetate and methanol. Typically, the reaction may be performed at room temperature or at low temperature (e.g., at 0° C. or less).

The compound of Formula 12d may be also prepared by performing a reductive amination with respect to a compound of Formula 12a to obtain a compound of Formula 12e; and then introducing an amine-protecting group to the compound of Formula 12e:

wherein, R₂, R₄, R₅, and R₈ are the same as defined in the above; X is halogen; and R₉ is hydrogen. P is an amine-protecting group such as tert-butoxycarbonyl.

The reductive amination of the compound of Formula 12a may be performed using a reducing agent such as sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride. The reductive amination may be in an organic solvent (e.g., alcohol) at room temperature or at low temperature (e.g., at 0° C. or less). And also, for improving reaction rate and/or yield, the reaction may be performed in the presence of acetic acid, etc.

The reaction for introducing an amine-protecting group to the compound of Formula 12e may be performed in an organic solvent such as dichloromethane, chloroform and 1,4-dioxane at room temperature or at low temperature (e.g., at 0° C. or less). And also, the reaction may be performed in the presence of a base such as triethylamine, diisopropylethylamine, and 4-dimethylaminopyridine.

The following examples and experimental examples are provided for illustration purposes only, and are not intended to limit the scope of the invention.

Preparation 1. 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine <Step 1> 2-(methylthio)-6-propylpyrimidin-4(3H)-one

A mixture of 6-n-propyl-2-thiouracil (25.0 g, 0.15 mol), sodium hydroxide (5.9 g, 0.15 mol), iodomethane (10.2 ml, 0.17 mol), and water (300 ml) was stirred at room temperature overnight and then filtered. The resulting solid was dried in vacuo to give the titled compound (25.0 g) as a white solid. The product was used in the subsequent reaction without further purification.

<Step 2> 2-(4-fluorophenylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (3.7 g, 0.02 mol) prepared in Step 1 and 4-fluoroaniline (6.7 g, 0.06 mol) was stirred at 160° C. overnight. The reaction mixture was cooled to room temperature, and then ethanol (50 ml) and charcoal (1 g) were added thereto. The reaction mixture was stirred for 1 hour and then filtered. The filtrate was concentrated under reduced pressure. Ethanol (20 ml) was added to the resulting residue, which was then stirred for 1 hour. The reaction mixture was filtered to give the titled compound as a gray solid.

¹H-NMR (400 MHz, CD₃OD) δ 7.70-7.50 (m, 2H), 7.07 (t, 2H), 5.75 (s, 1H), 2.43 (t, 2H), 1.70 (q, 2H), 0.98 (t, 3H)

<Step 3> 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine

2-(4-Fluorophenylamino)-6-propylpyrimidin-4(3H)-one (2.2 g, 8.9 mmol) prepared in Step 2 was added to phosphorus oxychloride (1.5 ml, 16.2 mmol), which was then stirred at 110° C. for 5 hours. After cooling to room temperature, ice water was added to the reaction mixture, which was then basified to pH 9 with sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate) to give 2.2 g of the titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.65-7.50 (m, 2H), 7.03 (t, 2H), 6.63 (s, 1H), 2.60 (t, 2H), 1.75 (q, 2H), 0.99 (t, 3H)

Preparation 2. (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine <Step 1> 2,4-dichloro-6-propylpyrimidine

Phosphorus oxychloride (100 ml) was slowly added at room temperature to 6-propyl-2-thiouracil (17.7 g, 0.1 mol), which was then stirred at 110° C. overnight. The reaction mixture was added to ice water and then neutralized with a saturated aqueous solution of sodium bicarbonate. The reaction mixture was extracted with dichloromethane. The organic layer was dried on anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=50/1) to give 10.3 g of the titled compound as pale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.73 (t, 2H), 1.78 (m, 2H), 0.99 (t, 3H)

<Step 2> (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine

2,4-Dichloro-6-propylpyrimidine (1.4 g, 7.3 mmol) prepared in Step 1 was dissolved in tetrahydrofuran (15 ml), and then (S)-2-(methoxymethyl)pyrrolidine (1.2 g, 10.4 mmol) was added thereto at room temperature. The reaction mixture was stirred at 60° C. overnight and then cooled to room temperature. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=10/1) to give 1.5 g of the titled compound as pale yellow oil. The product was used in the subsequent reaction without further purification.

Preparation 3. 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile <Step 1> 3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (6.4 g, 34.7 mmol) prepared in Step 1 of Preparation 1 and 3-aminobenzonitrile (12.3 g, 104.1 mmol) was stirred at 160° C. overnight. The reaction mixture was cooled to room temperature and then ethanol (50 ml) was added thereto. The reaction mixture was stirred for 1 hour and then filtered to give 3.5 g of the titled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ8.22 (s, 1H), 7.90-7.80 (m, 1H), 7.55-7.45 (m, 1H), 7.45-7.35 (m, 1H), 5.84 (s, 1H), 2.49 (t, 2H), 1.80-1.65 (m, 2H), 1.00 (t, 3H)

<Step 2> 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile

3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile (3.3 g, 13.0 mmol) prepared in Step 1 was added to phosphorus oxychloride (10 ml). The reaction mixture was stirred at 110° C. for 2 hours and then cooled to room temperature. The reaction mixture was added to ice water and then basified to pH 9 with sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=10/1) to give 3.2 g of the titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.18 (s, 1H), 7.75-7.65 (m, 1H), 7.50-7.20 (m, 3H), 6.72 (s, 1H), 2.65 (t, 2H), 1.78 (q, 2H), 1.01 (t, 3H)

Preparation 4. N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine <Step 1> 2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (1 g, 5.43 mmol) prepared in Step 1 of Preparation 1 and 6-aminoindole (789 mg, 5.97 mmol) was stirred at 150° C. overnight and then cooled to room temperature. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=40/1) to give 1.4 g of the titled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ 7.81 (s, 1H), 7.51 (d, 1H), 7.21 (d, 1H), 6.95 (dd, 1H), 6.42 (d, 1H), 5.70 (s, 1H), 2.44 (dd, 1H), 1.75-1.70 (m, 2H), 0.99 (t, 3H).

<Step 2> N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine

A solution of 2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one (1.2 g, 4.47 mmol) prepared in Step 1, phosphorus oxychloride (822 mg, 5.37 mmol), and diisopropylethylamine (1.9 ml, 10.7 mmol) in 1,4-dioxane (45 ml) was refluxed under stirring for 30 minutes. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=4/1) to give 1.1 g of the titled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.17 (brs, 1H), 8.05 (s, 1H), 7.53 (d, 1H), 7.25 (d, 1H), 7.11 (dd, 1H), 6.98 (dd, 1H), 6.58 (s, 1H), 6.48 (s, 1H), 2.59 (dd, 2H), 1.81-1.71 (m, 2H), 0.99 (t, 3H).

Preparation 5. (S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine

2,4-Dichloro-6-propylpyrimidine (1 g, 5.2 mmol) prepared in Step 1 of Preparation 2 was dissolved in ethanol (10 ml) and then (3S)-(−)-3-(methylamino)pyrrolidine (1 g, 10 mmol) was slowly added thereto at 0° C. The reaction mixture was stirred at room temperature overnight and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=40/1) to give 1 g of the titled compound as pale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.03 (s, 1H), 3.90-3.30 (m, 5H), 2.52 (t, 2H), 2.49 (s, 3H), 2.30-2.15 (m, 1H), 2.10-1.90 (m, 1H), 1.70 (q, 2H), 0.95 (t, 3H)

Preparation 6. 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile <Step 1> 2-methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (5 g, 27.1 mmol) prepared in Step 1 of Preparation 1 and 5-amino-2-methylbenzonitrile (7 g, 53 mmol) was stirred at 160° C. overnight. The reaction mixture was cooled to room temperature and then ethanol (30 ml) was added thereto. The reaction mixture was stirred for 1 hour and then filtered to give 6.3 g of the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.12 (d, 1H), 7.70-7.60 (m, 1H), 7.35 (d, 1H), 5.80 (s, 1H), 2.50-2.40 (m, 5H), 1.73 (q, 2H), 0.99 (t, 3H)

<Step 2> 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile

2-Methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile (6.3 g, 23.5 mmol) prepared in Step 1 was added to phosphorus oxychloride (10 ml). The reaction mixture was stirred at 110 for 2 hours and then cooled to room temperature. The reaction mixture was added to ice water and then basified to pH 9 with sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure to give 6 g of the titled compound as a yellow solid. The product was used in the subsequent reaction without further purification.

Preparation 7. N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine <Step 1> 2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (3 g, 16.3 mmol) prepared in Step 1 of Preparation 1 and 2-nitrobenzene-1,4-diamine (5 g, 32.6 mmol) was stirred at 160° C. overnight. The reaction mixture was cooled to 70° C. and then ethanol (30 ml) was added thereto. The reaction mixture was stirred for 1 hour and then filtered to give 4.5 g of the titled compound as a red solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.42 (s, 1H), 7.55-7.45 (m, 1H), 6.96 (d, 1H), 5.73 (s, 1H), 2.43 (t, 2H), 1.73 (q, 2H), 0.98 (t, 3H)

<Step 2> N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine

The titled compound (0.4 g) in the form of pale yellow solid was prepared in accordance with the same procedures as in Step 3 of Preparation 1, using 2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4(3H)-one (4.5 g, 15.5 mmol) prepared in Step 1.

¹H-NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.78 (d, 1H), 7.40 (brs, 1H), 7.19 (d, 1H), 6.81 (s, 1H), 2.70 (t, 2H), 1.81 (q, 2H), 1.03 (t, 3H)

Preparation 8. 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile <Step 1> 2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (8.8 g, 47.8 mmol) prepared in Step 1 of Preparation 1 and 5-amino-2-fluorobenzonitrile (7.9 g, 57.2 mmol) was stirred at 160° C. overnight. The reaction mixture was cooled to 70° C. and then ethanol (50 ml) was added thereto. The reaction mixture was stirred for 1 hour and then filtered to give 10 g of the titled compound as a pale brown solid. The product was used in the subsequent reaction without further purification

<Step 2> 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile

The titled compound (10.8 g) in the form of pale brown solid was prepared in accordance with the same procedures as in Step 3 of Preparation 1, using 2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile (10 g, 36.7 mmol) prepared in Step 1.

¹H-NMR (400 MHz, CDCl₃) δ 8.20-8.10 (m, 1H), 7.75-7.65 (m, 1H), 7.30-7.10 (m, 2H), 6.72 (s, 1H), 2.64 (t, 2H), 1.77 (q, 2H), 1.00 (t, 3H)

Preparation 9. 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine <Step 1> 6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-ol

A mixture of ethylpropionyl acetate (1.03 ml, 7.18 mmol), N-(4-fluorophenyl)guanidine (1 g, 6.53 mmol), sodium methoxide (0.39 g, 7.18 mmol), and ethanol (30 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was dissolved in water, acidified to pH 4 with a 1N hydrochloric acid solution, and then filtered. The resulting white solid (0.82 g) was dried in vacuo and then used in the subsequent reaction without further purification.

<Step 2> 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine

6-Ethyl-2-(4-fluorophenylamino)-pyrimidin-4-ol (0.82 g, 3.52 mmol) prepared in Step 1 was added to phosphorus oxychloride (1.5 ml, 16.2 mmol), which was then stirred at 110 for 1 hour. After cooling to room temperature, the reaction mixture was added to ice water and then basified to pH 9 with potassium hydroxide. The aqueous layer was extracted with dichloromethane. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=2/1) to give 432.2 mg of the titled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.18 (m, 2H), 7.08 (m, 2H), 6.63 (s, 1H), 2.61 (m, 2H), 1.23 (t, 3H)

Preparation 10. 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine <Step 1> 2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol

The titled compound (8.2 g) was prepared in accordance with the same procedures as in Step 1 of Preparation 9, using ethyl acetoacetate (10 g, 76.8 mmol), N-(4-fluorophenyl)guanidine (10.7 g, 69.8 mmol) and sodium methoxide (4.2 g, 71.8 mmol). The product was used in the subsequent reaction without further purification

<Step 2> 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine

The titled compound (4.5 g) in the form of white solid was prepared in accordance with the same procedures as in Step 2 of Preparation 9, using 2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol (8.2 g, 37.4 mmol) prepared in Step 1 and phosphorus oxychloride (15.9 ml, 172.0 mmol).

¹H-NMR (400 MHz, CDCl₃) δ 7.57-7.54 (m, 2H), 7.21 (brs, 1H), 7.05-7.01 (m, 2H), 6.64 (s, 1H), 2.39 (s, 3H)

Preparation 11. 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile <Step 1> 6-butyl-2-(methylthio)pyrimidin-4(3H)-one

A solution of ethyl 3-oxoheptanoate (10 g, 58.1 mmol), 2-methyl-2-thiopseudourea sulfate (11.7 g, 63.9 mmol), and sodium carbonate (9.8 g, 92.9 mmol) in water (116 ml) was stirred at room temperature for 2 days and then filtered. The resulting white solid was dried in vacuo to give the titled compound (11 g). The product was used in the subsequent step without further purification.

<Step 2> 3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A solution of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (500 mg, 2.52 mmol) prepared in Step 1 and 3-aminobenzonitrile (298 mg, 2.52 mmol) in n-butanol (3 ml) was stirred at 170° C. overnight. The reaction mixture was cooled to room temperature and then purified with silica gel column chromatography (dichloromethane/methanol=50/1) to give 310 mg of the titled compound as a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.47 (brs 1H), 8.27 (s, 1H), 7.80 (d, 1H), 7.37 (d, 1H), 5.88 (s, 1H), 2.58 (dd, 2H), 1.74-1.70 (m, 2H), 1.46-1.40 (m, 2H), 0.98 (t, 3H)

<Step 3> 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile

The titled compound in the form of pale yellow solid was prepared in accordance with the same procedures as in Step 2 of Preparation 9, using 3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile prepared in Step 2 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.19 (s, 1H), 7.69 (d, 1H), 7.42 (t, 1H), 7.33 (d, 1H), 7.26 (brs, 1H), 6.72 (s, 1H), 2.67 (t, 2H), 1.80-1.65 (m, 2H), 1.50-1.30 (m, 2H), 0.97 (t, 3H); (Yield: 80%)

Preparation 12. 5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile <Step 1> 5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrile

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (800 mg, 4.03 mmol) prepared in Step 1 of Preparation 11 and 5-amino-2-methylbenzonitrile (586 mg, 4.44 mmol) was stirred at 170° C. for 6 hours. The reaction mixture was cooled to room temperature and then purified with silica gel column chromatography (dichloromethane/methanol=100/1) to give 650 mg of the titled compound as a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.45 (brs 1H), 8.10 (s, 1H), 7.63 (d, 1H), 7.25 (d, 1H), 5.78 (s, 1H), 2.55-2.48 (m, 5H), 1.70-1.65 (m, 2H), 1.44-1.37 (m, 2H), 0.98 (t, 3H)

<Step 2> 5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Step 2 of Preparation 9, using 5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrile prepared in Step 1 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.08 (d, 1H), 7.57 (dd, 1H), 7.25 (m, 2H), 6.69 (s, 1H), 2.65 (dd, 2H), 2.51 (s, 3H), 1.75-1.68 (m, 2H), 1.45-1.36 (m, 2H), 0.96 (t, 3H); (Yield: 85%)

Preparation 13. (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide

A solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) prepared in Step 1 of Preparation 2, (3S)-(−)-3-acetamidopyrrolidine (1 g, 7.85 mmol), and diisopropylethylamine (1.8 ml, 10.46 mmol) in chloroform (52 ml) was stirred at 60° C. for 1 hour. The reaction mixture was cooled to room temperature, washed by water, and then extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 1.2 g of the titled compound as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 6.52 (brs, 1H), 6.02 (s, 1H), 4.59 (brs, 1H), 3.65-3.25 (m, 4H), 2.53 (dd, 2H), 2.28-2.24 (m, 1H), 2.02 (s, 3H), 2.02-1.98 (m, 1H), 1.74-1.65 (m, 2H), 0.96 (t, 3H)

Preparation 14. N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide

A solution of 2,4-dichloro-6-propylpyrimidine (200 mg, 1.05 mmol) prepared in Step 1 of Preparation 2,3-acetamidopyrrolidine (201 mg, 1.57 mmol), diisopropylethylamine (0.36 ml, 2.09 mmol) in chloroform (10.5 ml) was stirred at 40° C. for 1 hour. The reaction mixture was cooled to room temperature, washed by water, and then extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 205 mg of the titled compound as a white solid.

¹H NMR (400 MHz, CDCl₃) δ 6.52 (brs, 1H), 6.02 (s, 1H), 4.59 (brs, 1H), 3.65-3.25 (m, 4H), 2.53 (dd, 2H), 2.28-2.24 (m, 1H), 2.02 (s, 3H), 2.02-1.98 (m, 1H), 1.74-1.65 (m, 2H), 0.96 (t, 3H)

Preparation 15. (R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine

A solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) prepared in Step 1 of Preparation 2, (R)-2-methylpyrrolidine (668 mg, 7.85 mmol), diisopropylethylamine (1.8 ml, 10.46 mmol) in chloroform (52 ml) was stirred at 60° C. for 1 hour. The reaction mixture was cooled to room temperature, washed by water, and then extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=20/1) to give 910 mg of the titled compound as colorless liquid.

¹H NMR (400 MHz, CDCl₃) δ 6.00 (brs, 1H), 4.44-3.25 (m, 3H), 2.52 (dd, 2H), 2.12-1.95 (m, 3H), 1.75-1.66 (m, 3H), 1.22 (d, 3H), 0.96 (t, 3H)

Preparation 16. N¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine <Step 1> 2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4(3H)-one

The titled compound in the form of yellow solid was prepared in accordance with the same procedures as in Step 2 of Preparation 11, using 6-butyl-2-(methylthio)pyrimidin-4(3H)-one prepared in Step 1 of Preparation 11 and 2-nitrobenzene-1,4-diamine.

¹H-NMR (400 MHz, CD₃OD) δ 8.45 (s 1H), 7.47 (d, 1H), 6.96 (d, 1H), 5.73 (s, 1H), 4.61 (brs, 2H), 2.45 (d, 2H), 1.71-1.67 (m, 2H), 1.42-1.37 (m, 2H), 0.96 (t, 3H); (Yield: 85%)

<Step 2> N¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine

The titled compound in the form of pale yellow solid was prepared in accordance with the same procedures as in Step 2 of Preparation 9, using 2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4(3H)-one prepared in Step 1 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.77 (d, 1H), 7.48 (brs, 1H), 7.20 (d, 1H), 6.80 (s, 1H), 2.72 (dd, 2H), 1.77-1.71 (m, 2H), 1.46-1.40 (m, 2H), 0.98 (t, 3H); (Yield: 37%)

Preparation 17. (R)-3-hydroxypyrrolidine hydrochloride

Hydrogen chloride gas was added at 0° C. to a solution of (R)-1-(tert-butoxycarbonyl)-3-pyrrolidinol (3 g, 16.0 mmol) in ethyl acetate (100 ml). The reaction mixture was stirred at room temperature overnight and then filtered. The resulting white solid was dried in vacuo to give 1.3 g of the titled compound.

¹H-NMR (400 MHz, CD₃OD) δ 4.55 (m, 1H), 3.41-3.36 (m, 2H), 3.22 (m, 2H), 2.06-2.04 (m, 2H)

Preparation 18. (S)-3-methoxypyrrolidine <Step 1> (S)-3-methoxypyrrolidin-1-carboxylic acid tert-butyl ester

Sodium hydride (32 mg, 0.81 mmol, 60 wt %) was added at 0° C. to a solution of (S)-1-(tert-butoxycarbonyl)-3-pyrrolidinol (100 mg, 0.53 mmol) in N,N-dimethylformamide (2 ml). The reaction mixture was stirred for 30 minutes and iodomethane (99.7 μl, 1.60 mmol) was added thereto. The reaction mixture was stirred at room temperature overnight and then water was added thereto. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane. The resulting solution was washed with water, dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=5/2) to give 50 mg of the titled compound as colorless oil.

¹H-NMR (400 MHz, CDCl₃) δ 4.55 (m, 1H), 3.41-3.36 (m, 2H), 3.22 (m, 2H), 2.06-2.04 (m, 2H)

<Step 2> (S)-3-methoxypyrrolidine

Trifluoroacetic acid (0.5 ml) was added to a solution of (S)-3-methoxypyrrolidin-1-carboxylic acid tert-butyl ester (50 mg, 0.25 mmol) prepared in Step 1 in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane and then basified with an aqueous saturated solution of sodium bicarbonate. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure to give 7.5 mg of the titled compound as pale yellow oil. The product was used in the subsequent step without further purification.

Preparation 19. 2,5-diaminobenzonitrile

A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) and palladium/charcoal (10 mg, 10 wt %) in methanol (3 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/2) to give 160.3 mg of the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.79 (d, 1H), 6.72 (s, 1H), 6.61 (d, 1H), 4.01 (brs, NH), 3.45 (brs, NH)

Preparation 20. (S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol

The titled compound in the form of colorless oil was prepared in accordance with the same procedures as Step 2 of Preparation 2, using 2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 2 and (S)-(+)-2-pyrrolidinemethanol.

¹H-NMR (400 MHz, CDCl₃) δ 6.08 (s, 1H), 4.79 (br, 1H), 4.34 (br, 1H), 3.74 (m, 1H), 3.65 (m, 1H), 3.47-3.39 (m, 2H), 2.54 (t, 2H), 2.11-2.01 (m, 3H), 1.99 (br, 1H), 1.76 (m, 2H), 1.62 (s, 1H), 0.92 (t, 3H); (Yield: 47%)

Preparation 21. (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate

2,4-Dichloro-6-propylpyrimidine (1.5 g, 7.85 mmol) prepared in Step 1 of Preparation 2 was dissolved in ethanol (10 ml) and then (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (2.9 g, 15.7 mmol) was added thereto at 0° C. The reaction mixture was stirred at room temperature overnight and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 1.2 g of the titled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.67 (br, 1H), 4.33 (br, 1H), 3.84 (br, 2H), 3.24 (br, 2H), 2.54 (t, 2H), 2.26 (m, 1H), 1.93 (br, 1H), 1.71 (m, 2H), 1.45 (s, 9H), 0.95 (t, 3H)

Preparation 22. 1H-benzo[d]imidazol-5-amine

5-nitrobenzimidazole (200 mg, 1.2 mmol) was dissolved in a mixed solvent of methanol and tetrahydrofuran (1:1, 10 ml) and then palladium/charcoal (200 mg, 10 wt %) was added thereto. The reaction mixture was stirred at room temperature under hydrogen atmosphere (30 bar) for 3 hours and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure to give 150 mg of the titled compound as a pale yellow solid. The product was used in the subsequent reaction without further purification.

Preparation 23. 2-methylbenzene-1,4-diamine

The titled compound (54 mg) in the form of pale yellow solid was prepared in accordance with the same procedures as in Preparation 22, using 2-methyl-4-nitroaniline. The product was used in the subsequent reaction without further purification.

Preparation 24. (S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamide <Step 1> 6-butylpyrimidin-2,4-diol

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (2.1 g, 10.6 mmol) prepared in Step 1 of Preparation 11, acetic acid (15 ml) and water (7 ml) was refluxed under stirring for 2 days. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was dried in vacuo to give 1.7 g of the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, DMSO-d₆) δ 10.87 (brs, OH), 10.78 (brs, OH), 5.31 (s, 1H), 2.27 (m, 2H), 1.50 (m, 2H), 1.27 (m, 2H), 0.88 (t, 3H)

<Step 2> 4-butyl-2,6-dichloropyrimidine

A mixture of 6-butylpyrimidin-2,4-diol (1.7 g, 10.2 mmol) prepared in Step 1 and phosphorus oxychloride (5 ml) was refluxed under stirring for 1 hour. The reaction mixture was cooled to room temperature, added to ice water, and then basified to pH 8 with sodium bicarbonate. The aqueous layer was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/50) to give 1.435 g of the titled compound as brown oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.75 (t, 2H), 1.71 (m, 2H), 1.40 (m, 2H), 0.95 (t, 3H)

<Step 3> (S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamide

The titled compound in the form of colorless oil was prepared in accordance with the same procedures as in Preparation 13, using 4-butyl-2,6-dichloropyrimidine prepared in Step 2 and (3S)-(−)-3-acetamidopyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 7.25 (brs, NH), 6.02 (s, 1H), 4.54 (m, 1H), 3.64-3.41 (m, 4H), 2.54 (t, 2H), 2.24 (m, 1H), 2.04-2.01 (m, 1H+3H), 1.63 (m, 2H), 1.36 (m, 2H), 0.93 (t, 3H); (Yield: 56%)

Preparation 25. (S)-tert-butyl 1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate

Diisopropylethylamine (4.46 ml, 25.6 mmol) was added to a solution of 4-butyl-2,6-dichloropyrimidine (2.5 g, 12.1 mmol) prepared in Step 2 of Preparation 24 and (3S)-(−)-3-(methylamino)pyrrolidine (1.43 ml, 13.4 mmol) in chloroform (50 ml). The reaction mixture was stirred at 50° C. for 3 hours and then di-tert-butyldicarbonate (2.66 g, 12.2 mmol) was added thereto. The reaction mixture was stirred at room temperature overnight, washed with water, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/5) to give 3.29 g of the titled compound as colorless oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.81 (m, 1H), 3.50 (m, 4H), 2.80 (s, 3H), 2.56 (t, 2H), 2.17 (m, 1H), 1.67 (m, 2H), 1.48 (s, 9H+1H), 1.36 (m, 2H), 0.93 (t, 3H)

Preparation 26. (S)-tert-butyl 1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate

The titled compound in the form of pale yellow oil was prepared in accordance with the same procedures as in Preparation 25, using 4-butyl-2,6-dichloropyrimidine prepared in Step 2 of Preparation 24 and (3S)-(−)-3-(ethylamino)pyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 6.00 (s, 1H), 4.64 (m, 1H), 3.91-3.14 (m, 6H), 2.55 (t, 2H), 2.18 (m, 1H), 1.65 (m, 2H), 1.47 (s, 9H+1H), 1.37 (m, 2H), 1.15 (t, 3H), 0.92 (t, 3H); (Yield: 74%)

Preparation 27. (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide <Step 1> (S)-1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-amine

Diisopropylethylamine (1.09 ml, 6.28 mmol) was added to a solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) prepared in Step 1 of Preparation 2 and (S)-(−)-3-aminopyrrolidine (0.55 ml, 6.28 mmol) in ethanol (30 ml), which was then stirred at room temperature overnight. Dichloromethane was added to the reaction mixture, which was then washed with water. The organic layer was dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was used in the subsequent reaction without further purification.

<Step 2> (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide

A mixture of (S)-1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-amine (1.25 g, 5.23 mmol) prepared in Step 1, glycolic acid (0.44 g, 5.79 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.1 g, 5.79 mmol), 1-hydroxybenzotriazole hydrate (0.78 g, 5.79 mmol), diisopropylethylamine (1.8 ml, 10.3 mmol), and dichloromethane (30 ml) was stirred at room temperature for 3 days. The reaction mixture was diluted with dichloromethane, washed with water and an aqueous saturated solution of sodium bicarbonate, dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=20/1) to give 680 mg of the titled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.65 (s, NH), 6.03 (s, 1H), 4.65 (m, 1H), 4.14 (s, 2H), 3.80-3.41 (m, 4H), 2.54 (t, 2H), 2.39 (m, 1H), 2.10 (m, 1H), 1.72 (m, 2H), 0.96 (t, 3H)

Preparation 28. (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate

2,4-Dichloro-6-propylpyrimidine (2 g, 10.5 mmol) prepared in Step 1 of Preparation 2 and diisopropylethylamine (4.6 ml, 26.3 mmol) were dissolved in chloroform (100 ml) and (3S)-(−)-3-(methylamino)pyrrolidine (1.1 g, 10.5 mmol) was added thereto at room temperature. The reaction mixture was then stirred at 50° C. for 1 hour and then cooled to room temperature. Di-tert-butyl dicarbonate (2.5 g, 11.6 mmol) was added to the reaction mixture, which was then was stirred at 50° C. for 1 hour. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=3/1) to give 2.1 g of the titled compound as pale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.85 (brs, 1H), 4.00-3.10 (m, 4H), 2.80 (s, 3H), 2.54 (t, 2H), 2.30-2.00 (m, 2H), 1.80-1.60 (m, 2H), 1.48 (s, 9H), 0.96 (t, 3H)

Preparation 29. (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Preparation 28, using 2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 2 and (3S)-(−)-3-(ethylamino)pyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 6.01 (s, 1H), 4.63 (brs, 1H), 3.91 (brs, 1H), 3.70-3.10 (m, 5H), 2.53 (t, 2H), 2.30-2.05 (m, 2H), 1.72 (q, 2H), 1.48 (s, 9H), 1.15 (t, 3H), 0.95 (t, 3H); (Yield: 65%)

Preparation 30. 4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine <Step 1> 2-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (1.8 g, 9.8 mmol) prepared in Step 1 of Preparation 1 and 5-amino-2-fluorobenzotrifluoride (2 g, 11.2 mmol) was stirred at 160° C. overnight. The reaction mixture was cooled to 80° C. and then ethyl acetate (20 ml) was added thereto. The reaction mixture was refluxed under stirring for 1 hour and then filtered to give 2.2 g of the titled compound as a white solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.20 (s, 1H), 7.80-7.70 (m, 1H), 7.29 (t, 1H), 5.81 (s, 1H), 2.46 (t, 2H), 1.73 (q, 2H), 0.98 (t, 3H)

<Step 2> 4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine

A mixture of 2-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-6-propylpyrimidin-4(3H)-one (2.2 g, 7.0 mmol) prepared in Step 1 and phosphorus oxychloride (10 ml) was stirred at 110 overnight. The reaction mixture was cooled to room temperature, added to ice water, and then basified to pH 9 with sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=4/1) to give 2 g of the titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.27 (brs, 1H), 8.09 (s, 1H), 7.71 (d, 1H), 7.16 (t, 1H), 6.69 (s, 1H), 2.64 (t, 2H), 1.76 (q, 2H), 0.98 (t, 3H)

The synthetic method for the compounds (including the salt thereof) of the present invention is described in the following working examples. And also, the compounds of the following working examples and the NMR spectrum data are shown in the subsequent Tables 1-1 to 1-51.

Example 1

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20 mg, 0.08 mmol) prepared in Preparation 1 and pyrrolidine (25 mg, 0.35 mmol) in isopropanol (1 ml) was stirred at 100 overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=4/1) to give 20 mg of the product as a pale yellow solid.

Examples 2 to 24

The products of Examples 2 to 24 were prepared in accordance with the same procedures as in Example 1, using 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared in Preparation 1; and (S)-2-pyrrolidinemethanol, 3-pyrrolidinol, D-prolinol, DL-prolinol, 2-methylpyrrolidine, (S)-2-(methoxymethyl)pyrrolidine, (R)-2-(methoxymethyl)pyrrolidine, (S)-pyrrolidin-2-carboxamide, 3-acetamidopyrrolidine, (3R)-(+)-3-acetamidopyrrolidine, 2,2,2-trifluoro-N-(pyrrolidin-3-yl)acetamide, 3-(ethylamino)pyrrolidine, 3-(dimethylamino)pyrrolidine, (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine, (S)-(+)-2-(anilinomethyl)pyrrolidine, (3S)-(−)-3-acetamidopyrrolidine, (3S)(−)-3-(ethylamino)pyrrolidine, (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine, 3-aminopyrrolidine, 3-(diethylamino)pyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine, 3-(N-acetyl-N-methylamino)pyrrolidine, or (S)-3-pyrrolidinol.

Example 25

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20 mg, 0.08 mmol) prepared in Preparation 1 and 3-(ethylamino)pyrrolidine (0.25 g, 2.25 mmol) in isopropanol (3 ml) was stirred at 100 overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/2) and then dissolved in ethyl acetate (2 ml). Hydrogen chloride gas was added to the resulting solution and then filtered to give 0.33 g of the product as a white solid.

Example 26

A mixture of (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine (0.4 g, 1.4 mmol) prepared in Preparation 2 and 6-aminoindole (0.28 g, 2.1 mmol) in n-butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then filtered to give 0.25 g of the product as a pale yellow solid.

Example 27

A mixture of (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine (20 mg, 0.07 mmol) prepared in Preparation 2 and 5-aminoindole (30 mg, 0.23 mmol) in n-butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 5.2 mg of the product as a pale yellow solid.

Examples 28 to 46

The products of Examples 28 to 46 were prepared in accordance with the same procedures as in Example 27, using (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine prepared in Preparation 2; and 4-methoxyaniline, 3-methoxyaniline, 3-chloroaniline, 4-fluoro-3-nitroaniline, 3-nitroaniline, 4-chloro-3-nitroaniline, 3-aminobenzonitrile, 3-(methylthio)aniline, 3-(trifluoromethyl)aniline, 7-amino-4-methyl-2H-chromen-2-one, 5-chloro-2-methylaniline, 4-amino-2-chlorotoluene, 4-methyl-3-nitroaniline, 4-fluoro-3-(trifluoromethyl)aniline, 2-(trifluoromethyl)benzene-1,4-diamine, 5-amino-2-fluorobenzonitrile, 5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared in Preparation 19, or 2-nitro-1,4-phenylenediamine.

Example 47

(S)-tert-Butyl 1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate (10 mg, 0.02 mmol) prepared in Example 19 was dissolved in ethyl acetate (1 ml) and then hydrogen chloride gas was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 7 mg of the product as a white solid.

Examples 48 to 58

The products of Examples 48 to 58 were prepared in accordance with the same procedures as in Example 1, using 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared in Preparation 3; and (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine, 3-(diethylamino)pyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine, 3-(N-acetyl-N-methylamino)pyrrolidine, (S)-3-pyrrolidinol, (R)-(−)-2-methylpyrrolidine, (3S)-(−)-3-acetamidopyrrolidine, (3S)-(−)-3-(ethylamino)pyrrolidine, (3S)-(−)-3-(N-tert-butoxycarbonylaminomethyl)pyrrolidine, (R)-3-hydroxypyrrolidine hydrochloride prepared in Preparation 17, or (S)-3-methoxypyrrolidine prepared in Preparation 18.

Example 59

The product in the form of white solid was prepared in accordance with the same procedures as in Example 25, using 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared in Preparation 3 and 3-(methylamino)pyrrolidine.

Example 60

The product in the form of white solid was prepared in accordance with the same procedures as in Example 47, using (S)-tert-Butyl 1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate prepared in Example 48.

Example 61

A mixture of (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride (20 mg, 0.05 mmol) prepared in Example 60, butyric acid (7 mg, 0.08 mol), (benzotriazole-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (31.8 mg, 0.06 mmol), diisopropylethylamine (25.9 mg, 0.2 mmol), and N,N-dimethylformamide (1 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with brine, dried on anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 10.5 mg of the product as a pale yellow solid.

Examples 62 to 82

The products of Examples 62 to 82 were prepared in accordance with the same procedures as in Example 61, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 60; and cyclopentanecarboxylic acid, 1-piperidinepropionic acid, benzoic acid, 4-fluorobenzoic acid, phenylacetic acid, 4-fluorophenylacetic acid, 3-phenoxypropionic acid, 3-isobutoxypropanoic acid, 2-(4-benzylpiperazin-1-yl)acetic acid, 2-(piperidin-1-yl)acetic acid, 3-benzoylpropionic acid, 4-aminophenylacetic acid, cyclopentylacetic acid, methoxyacetic acid, 2-pyridylacetic acid, 3-pyridylacetic acid, 4-pyridylacetic acid, trans-styrylacetic acid, 2-thiopheneacetic acid, isobutanoic acid or 3,3,3-trifluoropropanoic acid.

Example 83

A mixture of 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile (20 mg, 0.07 mmol) prepared in Preparation 3,2-pyrrolidone (9.4 mg, 0.11 mmol), palladium acetate (0.16 mg, 0.7 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.3 mg, 2.1 μmol), cesium carbonate (71.4 mg, 0.22 mmol), and 1,4-dioxane (1 ml) was stirred at 110° C. overnight and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=4/1) to give 5 mg of the product as a pale yellow solid.

Example 84

(S)-3-[4-(3-Aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride (20 mg, 0.05 mmol) prepared in Example 60 and hexylaldehyde (5 mg, 0.05 mmol) in methanol (1 ml) was stirred at room temperature for 30 minutes and sodium cyanoborohydride (9.4 mg, 0.15 mmol) was added thereto. The reaction mixture was stirred at room temperature for 3 hours and then an aqueous saturated solution of sodium bicarbonate was added thereto to terminate the reaction. The reaction mixture was extracted with ethyl acetate. The organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 10 mg of the product as a pale yellow solid.

Examples 85 to 117

The products of Examples 85 to 117 were prepared in accordance with the same procedures as in Example 84, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 60; and propionaldehyde, cyclohexanecarboxaldehyde, benzaldehyde, phenylacetaldehyde, 3-phenylpropionaldehyde, 3-fluorobenzaldehyde, 4-hydroxybenzaldehyde, 4-ethylbenzaldehyde, 3-methylbutanal, pentanal, 2-methylbutanal, 2-methylpropanal, 4-methoxybenzaldehyde, 4-fluorobenzaldehyde, cyclopropanecarboxaldehyde, cyclopropanecarboxaldehyde (2 eq.), 2-pyridinecarboxaldehyde, 3-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde, 2-ethylbutanal, pivaldehyde, 2-fluorobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, 4-(trifluoromethyl)benzaldehyde, 4-acetoxybenzaldehyde, 4-(dimethylamino)benzaldehyde, pyrrole-2-carboxaldehyde, thiophene-2-carboxaldehyde, thiophene-3-carboxaldehyde, butanal (2 eq.), 3-(methylthio)propionaldehyde (2 eq.), butanal, or 3-(methylthio)propionaldehyde.

Example 118

(S)-3-{4-Propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile (20 mg, 0.05 mmol) prepared in Example 85 was dissolved in ethyl acetate (1 ml) and hydrochloric acid was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 15.5 mg of the product as a white solid.

Examples 119

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Example 99.

Examples 120

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Example 50.

Example 121

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 1, using N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared in Preparation 4 and (3S)-(−)-3-(methylamino)pyrrolidine.

Example 122

A mixture of (S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine (0.4 g, 1.57 mmol) prepared in Preparation 5 and 6-aminoindole (0.21 g, 1.57 mmol) in n-butanol (2 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then filtered. The resulting solid was dried to give 0.2 g of the product as a pale yellow solid.

Example 123

A mixture of (S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine (1 g, 3.93 mmol) in prepared in Preparation 5 and 2-(trifluoromethyl)-1,4-phenylenediamine (0.7 g, 3.93 mmol) in n-butanol (10 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was diluted with dichloromethane, washed with an aqueous saturated solution of sodium bicarbonate, dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=10/1) and then dissolved in ethyl acetate (10 ml). Hydrogen chloride gas was added to the solution and then filtered to give 0.4 g of the product as a white solid.

Example 124

A mixture of (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride (20 mg, 0.05 mmol) prepared in Example 60, triethylamine (20 mg, 0.2 mmol), isopropylsulfonyl chloride (8 mg, 0.05 mmol), and N,N-dimethylformamide (1 ml) was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with brine, dried on anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 9.5 mg of the product as a pale yellow solid.

Examples 125 and 126

The products of Examples 125 and 126 were prepared in accordance with the same procedures as in Example 124, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 60; and methanesulfonyl chloride or 4-fluorobenzenesulfonyl chloride.

Example 127

A solution of (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride (30 mg, 0.08 mmol) prepared in Example 60 and methyl ethyl ketone (18 mg, 0.25 mmol) in methanol (0.8 ml) was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (71.2 mg, 0.34 mmol) and a catalytic amount of acetic acid were added thereto. The reaction mixture was stirred at room temperature overnight and then an aqueous saturated solution of sodium bicarbonate was added thereto to terminate the reaction. The reaction mixture was extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=50/1) to give 32 mg of the product as a white solid.

Examples 128 to 145

The products of Examples 128 to 145 were prepared in accordance with the same procedures as in Example 127, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 60; and 3-pentanone, 2,6-dimethyl-4-heptanone, 4,4-dimethyl-2-pentanone, 3-hydroxy-3-methyl-2-butanone, 4-heptanone, 2-hexanone, 5-methyl-2-hexanone, cyclohexanone, tert-butyl 2-oxoethylcarbamate, 1-benzyl-4-piperidinone, acetone, 1-benzoyl-4-piperidone, 1-acetyl-4-piperidone, cydooctanone, cydobutanone, cyclopentanone, tert-butyl 3-oxoazetidine-1-carboxylate, or 2-benzyloxyacetaldehyde.

Example 146

A mixture of (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride (18 mg, 0.05 mmol) prepared in Example 60, propionic acid (4.6 μl, 0.06 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (11.8 mg, 0.06 mmol), 1-hydroxybenzotriazole hydrate (8.3 mg, 0.06 mmol), diisopropylethylamine (19.4 μl, 0.11 mmol), and dichloromethane (1 ml) was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with water and an aqueous saturated solution of sodium bicarbonate, dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=70/1) to give 13.4 mg of the product as a white solid.

Examples 147 to 167

The products of Examples 147 to 167 were prepared in accordance with the same procedures as in Example 146, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 60; and pivalic acid, 2,2-dimethylbutyric acid, tiglic acid, hexanoic acid, 3-phenylpropionic acid, indole 3-acetic acid, 2-hydroxyisobutyric acid, 3-(4-methoxyphenyl)propionic acid, 3-(4-hydroxyphenyl)propionic acid, levulinic acid, glycolic acid, benzyloxyacetic acid, phenoxyacetic acid, N,N-dimethylglycine hydrochloride, 3-(dimethylamino)propionic acid hydrochloride, 4-(dimethylamino)butyric acid hydrochloride, ethoxyacetic acid, 2-(2-methoxyethoxy)acetic acid, benzyloxycarbonylaminoacetic acid, N-(tert)-butoxycarbonyl-L-γ-aminobutyric acid, or piperidine-1,4-dicarboxylic acid mono tert-butyl ester.

Example 168

A solution of (R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine (20 mg, 0.083 mmol) prepared in Preparation 15 and 5-amino-2-methylbenzonitrile (12.6 mg, 0.091 mmol) in n-butanol (0.5 ml) was reacted in a microwave reactor (450 W) for 40 minutes. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=50/1) and then dissolved in ethyl acetate (1 ml). Hydrogen chloride gas was added to the solution, which was then stirred at room temperature for 1 hour. The reaction mixture was filtered to give 9 mg of the product as a white solid.

Example 169

The product in the form of white solid was prepared in accordance with the same procedures as in Example 168, using (R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared in Preparation 15 and 2,5-diaminobenzonitrile prepared in Preparation 19.

Examples 170 and 171

The products of Examples 170 and 171 were prepared in accordance with the same procedures as in Example 1, using 5-(4-chloro-6-pro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile prepared in Preparation 6; and (3S)-(−)-3-(methylamino)pyrrolidine or (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 172

A mixture of 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile (20 mg, 0.07 mmol) prepared in Preparation 6 and (3S)-(−)-3-(ethylamino)pyrrolidine (8 mg, 0.07 mmol) in isopropanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then filtered. The resulting pale yellow solid was dried to give to 12 mg of the product.

Example 173

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 172, using 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile prepared in Preparation 6 and 3-(ethylamino)pyrrolidine.

Example 174

A solution of 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile (200 mg, 0.7 mmol) prepared in Preparation 6 and (3S)-(−)-3-(methylamino)pyrrolidine (69.9 mg, 0.7 mmol) in isopropanol (1.4 ml) was reacted in a microwave reactor (450 W) for 30 minutes. The reaction mixture was cooled to room temperature and then filtered to give 209 mg of the product as a pale gray solid.

Examples 175 and 176

The products of Examples 175 and 176 were prepared in accordance with the same procedures as in Example 1, using N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine prepared in Preparation 7; and (3S)-(−)-3-(methylamino)pyrrolidine or (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 177

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 172, using N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine prepared in Preparation 7 and (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 178

The product in the form of white solid was prepared in accordance with the same procedures as in Example 172, using 3-(4-chloro-6-propylpyrimidin-2-yl)benzonitrile prepared in Preparation 3 and (3S)-(−)-3-(methylamino)pyrrolidine.

Example 179

The product in the form of white solid was prepared in accordance with the same procedures as in Example 47, using (S)-tert-butyl {1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methylcarbamate prepared in Example 56.

Examples 180 and 181

The products of Examples 180 and 181 were prepared in accordance with the same procedures as in Example 172, using 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile prepared in Preparation 8; and (3S)-(−)-3-(methylamino)pyrrolidine or (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 182

A solution of 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile (0.2 g, 0.67 mmol) prepared in Preparation 8 and 3-(tert-butoxycarbonylamino)pyrrolidine (0.2 g, 1.0 mmol) in isopropanol (3 ml) was stirred at 100 overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) and then dissolved in ethyl acetate (1 ml). Hydrogen chloride gas was added to the solution, which was then stirred at room temperature for 1 hour. The reaction mixture was filtered to give 0.1 g of the product as a white solid.

Example 183

The product in the form of white solid was prepared in accordance with the same procedures as in Example 1, using 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine prepared in Preparation 10 and pyrrolidine.

Example 184 <Step 1> (2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylic acid

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (50 mg, 0.19 mmol) prepared in Preparation 1, trans-4-hydroxy-L-proline (27.3 mg, 0.21 mmol), and diisopropylethylamine (49 μl, 0.38 mmol) in isopropanol (1.0 ml) was reacted in a microwave reactor (500 W) for 30 minutes. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=30/1) to give 30 mg of the titled compound.

<Step 2> (2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylic acid methyl ester

A solution of (2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylic acid (30 mg, 0.08 mmol) prepared in Step 1 and a catalytic amount of sulfuric acid in methanol (3 ml) was refluxed under stirring overnight. The reaction mixture was neutralized with an aqueous saturated solution of sodium bicarbonate and then extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated to give 30 mg of the titled compound. The resulting product was used in the subsequent reaction without further purification.

<Step 3> (3R,5S)-1-[2-(4-fluorophenyl)-6-propylpyrimidin-4-yl]-5-(hydroxymethyl)pyrrolidin-3-ol

A solution of (2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylic acid methyl ester (20 mg, 0.05 mmol) prepared in Step 2 and sodium borohydride (12.1 mg, 0.32 mmol) in ethanol (1 ml) was stirred for 3 hours and then an aqueous saturated solution of ammonium chloride was added thereto to terminate the reaction. The reaction mixture was extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=30/1) to give 14 mg of the titled compound as a white solid.

Example 185

A mixture of N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine (13 mg, 0.05 mmol) prepared in Preparation 4, (S)-pyrrolidin-2-ylmethanol (9.1 mg, 0.09 mmol), diisopropylethylamine (17.6 mg, 14 mol) in isopropanol (0.5 ml) was reacted in a microwave reactor (300 W) for 2 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=2/1) to give 17.1 mg of the product as a yellow liquid.

Examples 186 to 192

The products of Examples 186 to 192 were prepared in accordance with the same procedures as in Example 185, using N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared in Preparation 4; and (R)-pyrrolidin-2-ylmethanol, pyrrolidin-2-ylmethanol, (R)-2-(methoxymethyl)pyrrolidine, (S)-2-(methoxymethyl)pyrrolidine, 2-methylpyrrolidine, (S)-methylpyrrolidine-2-carboxylate, or N-(pyrrolidin-3-yl)acetamide.

Example 193

The product in the form of white solid was prepared in accordance with the same procedures as in Example 26, using (S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol prepared in Preparation 20 and 6-aminoindole.

Examples 194 to 215

The products of Examples 194 to 215 were prepared in accordance with the same procedures as in Example 27, using (S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol prepared in Preparation 20; and 3-aminobenzonitrile, 3-(methylthio)aniline, 4-chloro-3-nitroaniline, 5-aminoindole, 1H-benzo[d]imidazol-5-amine prepared in Preparation 22, 5-amino-2-(trifluoromethyl)benzimidazole, 4-methoxyaniline, 3-chloroaniline, 3-methoxyaniline, 3-(trifluoromethyl)aniline, 5-chloro-2-methylaniline, 5-methoxy-2-methylaniline, 4-amino-2-chlorotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline, 6-aminoquinoline, 4-methyl-3-nitroaniline, 2-(trifluoromethyl)benzene-1,4-diamine, 3-nitro-1,4-phenylenediamine, 5-amino-2-methylbenzonitrile, 5-amino-2-fluorobenzonitrile, or 2,5-diaminobenzonitrile prepared in Preparation 19.

Example 216

3-Aminoquinoline (22 mg, 0.15 mmol) was added to a mixture of (S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol (30 mg, 0.12 mmol) prepared in Preparation 20, palladium acetate (0.5 mg, 2 mol %), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (2.1 mg, 3 mol %), cesium carbonate (78 mg, 0.24 mmol), and anhydrous 1,4-dioxane (1 ml). The reaction mixture was stirred in a microwave reactor (600 W) for 1 hour. The reaction mixture was cooled to room temperature, suspended in dichloromethane, and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 29.8 mg of the product as a pale yellow solid.

Example 217 <Step 1> (S)-1-(6-{4-[2-(hydroxylmethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone

The titled compound in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 27, using (S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol prepared in Preparation 20 and 1-acetyl-6-aminoindoline. The product was used in the subsequent reaction without further purification.

<Step 2> (S)-2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol

A mixture of (S)-1-(6-{4-[2-(hydroxylmethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone (45.7 mg, 0.12 mmol) prepared in Step 1 and 3N hydrochloric acid solution (1.5 ml) was refluxed under stirring for 2 hours. The reaction mixture was cooled to room temperature, basified to pH 8-9 with a 2N sodium hydroxide solution, and then extracted with dichloromethane. The resulting organic layer was dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=40/1) to give 19.2 mg of the titled compound as colorless oil.

Example 218

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Example 135.

Example 219

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Example 138.

Example 220

The product in the form of white solid was prepared in accordance with the same procedures as in Example 47, using (S)-tert-butyl 2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}ethylcarbamate prepared in Example 136.

Example 221

A solution of (S)-3-{4-[3-(1-benzylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile (110 mg, 0.22 mmol) prepared in Example 137 and palladium/charcoal (11 mg, 10 wt %) in methanol (2.2 ml) was stirred at room temperature under hydrogen atmosphere for 5 hours and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=10/1) to give 28 mg of the product as a white solid.

Example 222

A solution of (S)-3-{4-[3-(piperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile (15 mg, 0.04 mmol) prepared in Example 221 and butyraldehyde (2.7 mg, 0.04 mmol) in methanol (0.4 ml) was stirred at room temperature for 30 minutes and then sodium triacetoxyborohydride (15.7 mg, 0.08 mmol) was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then an aqueous saturated solution of sodium bicarbonate was added thereto to terminate the reaction. The reaction mixture was extracted with dichloromethane. The resulting organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=50/1) to give 4.0 mg of the product as a white solid.

Example 223

A solution of 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile (20 mg, 0.07 mmol) prepared in Preparation 11 and (S)—N-(pyrrolidin-3-yl)acetamide (9.8 mg, 0.08 mmol) in isopropanol (0.3 ml) was reacted in a microwave reactor (450 W) for 30 minutes. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=50/1) to give 26.7 mg of the product as a white solid.

Examples 224 to 227

The products of Examples 224 to 227 were prepared in accordance with the same procedures as in Example 223, using 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile prepared in Preparation 11; and (S)-pyrrolidin-2-ylmethanol, (R)-2-methylpyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine, or (S)-tert-butyl pyrrolidin-3-ylcarbamate.

Examples 228 to 232

The products of Examples 228 to 232 were prepared in accordance with the same procedures as in Example 223, using 5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile prepared in Preparation 12; and (S)—N-(pyrrolidin-3-yl)acetamide, (S)-pyrrolidin-2-ylmethanol, (R)-2-methylpyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine, or (S)-tert-butyl pyrrolidin-3-ylcarbamate.

Example 233

The product in the form of white solid was prepared in accordance with the same procedures as in Example 47, using (S)-tert-butyl 1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamate prepared in Example 227.

Example 234

The product in the form of white solid was prepared in accordance with the same procedures as in Example 47, using (S)-tert-butyl 1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl)pyrrolidin-3-ylcarbamate prepared in Example 232.

Examples 235 to 237

The products of Examples 235 to 237 were prepared in accordance with the same procedures as in Example 127, using (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Example 233; and acetone, acetaldehyde (2 eq.), or cyclopropanecarboxaldehyde.

Examples 238 to 240

The products of Examples 238 to 240 were prepared in accordance with the same procedures as in Example 127, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 234; and acetone, acetaldehyde (2 eq.), or cyclopropanecarboxaldehyde.

Example 241

A solution of (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide (20 mg, 0.07 mmol) prepared in Preparation 13 and 4-chloro-3-nitroaniline (13.5 mg, 0.08 mmol) in n-butanol (0.5 ml) was reacted in a microwave reactor (450 W) for 50 minutes. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=50/1) to give 26.1 mg of the product as a pale yellow solid.

Examples 242 to 259

The products of Examples 242 to 259 were prepared in accordance with the same procedures as in Example 241, using (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 13; and 3-(methylthio)aniline, 6-aminoindole, 3-(trifluoromethyl)aniline, 7-amino-4-methyl-2H-chromen-2-one, 2-chloro-4-aminotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline, 4-methyl-3-nitroaniline, benzyl 5-amino-2-methoxyphenylcarbamate, 5-amino-2-fluorobenzonitrile, 5-amino-2-methylbenzonitrile, 4-fluoro-3-(trifluoromethyl)aniline, 2-nitrobenzene-1,4-diamine, 5-chloro-2-methylaniline, 3-aminobenzamide, 3-amino-N-methylbenzamide, 3-aminobenzylamine, or 3-amino-4-chlorobenzamide.

Example 260

A solution of (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide (20 mg, 0.08 mmol) prepared in Preparation 13 and 2,5-diaminobenzonitrile (9.5 mg, 0.07 mmol) prepared in Preparation 19 in n-butanol (0.5 ml) was reacted in a microwave reactor (450 W) for 40 minutes. The reaction mixture was cooled to room temperature and then filtered to give 17.1 mg of the product as a yellow solid.

Examples 261 and 262

The products of Examples 261 and 262 were prepared in accordance with the same procedures as in Example 260, using (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 13; and 2-(trifluoromethyl)-1,4-phenylenediamine or 3,5-diaminobenzonitrile.

Examples 263 to 273

The products of Examples 263 to 273 were prepared in accordance with the same procedures as in Example 26, using (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 13; and 6-aminoindole, 5-chloro-2-methylaniline, 4-fluoro-3-(trifluoromethyl)aniline, 4-fluoro-1,3-diaminobenzene, 3-(trifluoromethyl)aniline, 5-(trifluoromethyl)-1,3-phenylenediamine, 3-nitroaniline, 1,4-phenylenediamine, 5-amino-2-chlorophenol, 4-aminosalicylic acid, or 5-aminosalicylic acid.

Examples 274 to 282

The products of Examples 274 to 282 were prepared in accordance with the same procedures as in Example 27, using (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 13; and 5-amino-o-cresol, 4-amino-2-chlorophenol, 4-amino-o-cresol, 4-amino-2-fluorophenol, 3-hydroxy-4-methoxyaniline, 3-methoxy-4-methylaniline, 4-methyl-3-(trifluoromethyl)aniline, 3,4-dimethylaniline, or 3-fluoro-4-methylaniline.

Example 283

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 248.

Example 284

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 249.

Example 285

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 252.

Example 286

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 254.

Example 287

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 54.

Example 288

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 241.

Example 289

The product in the form of white solid was prepared in accordance with the same procedures as in Example 221, using (S)-benzyl 5-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamate prepared in Example 250.

Example 290

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 241.

Example 291

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 248.

Example 292

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 249.

Example 293

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 260, using N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 14 and 2-nitrobenzene-1,4-diamine.

Examples 294 to 309

The products of Examples 294 to 309 were prepared in accordance with the same procedures as in Example 27, using N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 14; and 3-aminobenzonitrile, 3-nitroaniline, 4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline, 3-methoxyaniline, 5-methoxy-2-methylaniline, 4-methoxyaniline, 3-(trifluoromethyl)aniline, 3-chloroaniline, 5-chloro-2-methylaniline, 2-chloro-4-aminotoluene, 3-(methylthio)aniline, 5-aminoindole, 5-amino-2-(trifluoromethyl)benzimidazole, 6-aminoquinoline, or 7-amino-4-methyl-2H-chromen-2-one.

Example 310

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 216, using N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 14 and 3-aminoquinoline.

Examples 311 and 312 The products of Examples 311 and 312 were prepared in accordance with the same procedures as in Example 26, using N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 14 and 2,5-diaminobenzonitrile prepared in Preparation 19 or 4-fluoro-1,3-phenylenediamine.

Examples 313 to 329

The products of Examples 313 to 329 were prepared in accordance with the same procedures as in Example 241, using (R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared in Preparation 15; and 4-chloro-3-nitroaniline, 3-(methylthio)aniline, 6-aminoindole, 3-(trifluoromethyl)aniline, 7-amino-4-methyl-2H-chromen-2-one, 2-chloro-4-aminotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline, 4-methyl-3-nitroaniline, 4-fluoro-3-(trifluoromethyl)aniline, 2-(trifluoromethyl)-1,4-phenylenediamine, benzyl 5-amino-2-methoxyphenylcarbamate, 5-amino-2-fluorobenzonitrile, 5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared in Preparation 19, 2-nitrobenzene-1,4-diamine, or 1-(6-aminoindolin-1-yl)ethanone.

Example 330

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 216, using (R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared in Preparation 15 and 5-chloro-2-methylaniline.

Example 331

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (R)-benzyl 2-methoxy-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]phenylcarbamate prepared in Example 324.

Example 332

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (R)—N-(4-chloro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine prepared in Example 313.

Example 333

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine prepared in Example 320.

Example 334

The product in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 221, using (R)—N-(4-methyl-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine prepared in Example 321.

Example 335

A solution of (S)-3-(4-{3-[2-(benzyloxy)ethylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile (60 mg, 0.13 mmol) prepared in Example 145, palladium/charcoal (12 mg, 10 wt %) and a catalytic amount of conc. HCl in methanol (6.0 ml) was stirred at room temperature under hydrogen atmosphere overnight and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (1 ml) and then hydrogen chloride gas was added thereto. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 39.0 mg of the product as a white solid.

Example 336

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-5-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile prepared in Example 229.

Examples 337 and 338

The products of Examples 337 and 338 were prepared in accordance with the same procedures as in Example 223, using N¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine prepared in Preparation 16; and (S)—N-(pyrrolidin-3-yl)acetamide or (3S)-(−)-3-(methylamino)pyrrolidine.

Example 339

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile prepared in Example 111.

Example 340

The product in the form of white solid was prepared in accordance with the same procedures as in Example 168, using (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine prepared in Preparation 2 and 2-nitro-1,4-phenylenediamine.

Example 341

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (S)-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol prepared in Example 208.

Example 342

A mixture of (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate (30 mg, 0.09 mmol) prepared in Preparation 21, 5-(trifluoromethyl)benzene-1,3-diamine (19.4 mg, 0.11 mmol), and n-butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=20/1) and then dissolved in ethyl acetate (2 ml). Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 11.1 mg of the product as a white solid.

Examples 343 to 361

The products of Examples 343 to 361 were prepared in accordance with the same procedures as in Example 342, using (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate prepared in Preparation 21; and 2-methylbenzene-1,4-diamine prepared in Preparation 23, 4-chloro-3-nitroaniline, 3-(methylthio)aniline, 6-aminoindole, 3-(trifluoromethyl)aniline, 5-chloro-2-methylaniline, 4-amino-2-chlorotoluene, 3-nitroaniline, 4-methyl-3-nitroaniline, 2-(trifluoromethyl)benzene-1,4-diamine, 5-amino-2-fluorobenzonitrile, 5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared in Preparation 19, (5-amino-2-methoxyphenyl)carbamic acid benzyl ester, 4-fluoro-3-(trifluoromethyl)aniline, 4-fluoro-3-nitroaniline, 2-nitro-1,4-phenylenediamine, 3,5-bis(trifluoromethyl)aniline or 3,5-dimethoxyaniline.

Example 362

A solution of (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate (30 mg, 0.09 mmol) prepared in Preparation 21, 3,5-diaminobenzonitrile (14.6 mg, 0.11 mmol) in butanol (1 ml) was refluxed under stirring overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. Hydrochloric acid was added at 0° C. to the resulting residue. The suspension was stirred at room temperature for 2 hours and then filtered. The resulting solid was washed with ethyl acetate. The solid was dissolved in dichloromethane (10 ml) and then an aqueous saturated solution of sodium bicarbonate was added thereto. The solution was stirred for 30 minutes and then extracted with dichloromethane. The organic layer was dried on anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 11.7 mg of the titled compound as a white solid.

Example 363

The product in the form of white solid was prepared in accordance with the same procedures as in Example 362, using (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate prepared in Preparation 21 and 3-aminobenzenesulfonamide.

Example 364

Palladium/charcoal (25 mg, 10 wt %) was added to a solution of (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine (20 mg, 0.06 mmol) prepared in Example 32 in methanol (2 ml). The reaction mixture was stirred at room temperature under hydrogen atmosphere (30 bar) for 3 hours and then filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 4.4 mg of the product as a pale yellow solid.

Example 365

The product (4.4 mg) in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 364, using (S)—N-(4-fluoro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine prepared in Example 31.

Example 366

The product (7.2 mg) in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 364, using (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine prepared in Example 40.

Example 367 <Step 1> (S)-benzyl 2-methoxy-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}phenylcarbamate

The titled compound (15 mg) in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 27, using (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine prepared in Preparation 2 and (5-amino-2-methoxyphenyl)carbamic acid benzyl ester.

<Step 2> (S)-4-methoxy-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine

The titled compound (7.8 mg) in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 364, using (S)-benzyl 2-methoxy-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}phenylcarbamate prepared in Step 1.

Example 368

The titled compound in the form of pale yellow oil was prepared in accordance with the same procedures as in Example 217, using (S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine prepared in Preparation 2 and 1-acetyl-6-aminoindoline.

Example 369

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 364, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 351.

Example 370 <Step 1> (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine

The titled compound in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 364, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 358.

<Step 2> (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine dihydrochloride

The titled compound in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine prepared in Step 1.

Example 371

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (S)-3-amino-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-amino]benzonitrile prepared in Example 362.

Example 372

Cyclopropanecarboxaldehyde (6.51 ml, 0.09 mmol) was added to a solution of (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-chloro-3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride (30 mg, 0.07 mmol) prepared in Example 344 in methanol (1 ml). The reaction mixture was stirred at room temperature for 30 minutes and then sodium cyanoborohydride (6.84 mg, 0.11 mmol) was added thereto. The reaction mixture was stirred at room temperature overnight and then a 1N hydrochloric acid solution was added thereto. The reaction mixture was stirred for 30 minutes, neutralized with a 1N sodium hydroxide solution, and then extracted with ethyl acetate. The organic layer was dried on anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/methanol=20/1) to give 5.9 mg of the product as a pale yellow solid.

Example 373

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 358.

Example 374

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 351.

Example 375

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 350.

Example 376

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile dihydrochloride prepared in Example 353.

Example 377

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 354.

Example 378

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 345.

Example 379

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine dihydrochloride prepared in Example 347.

Example 380

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(5-chloro-2-methylphenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 348.

Example 381

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-chloro-4-methylphenyl)-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 349.

Example 382

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 372, using (S)-4-(3-aminopyrrolidin-1-yl)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine dihydrochloride prepared in Example 357.

Example 383

The product in the form of white solid was prepared in accordance with the same procedures as in Example 364, using (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine prepared in Example 374.

Example 384

The product in the form of white solid was prepared in accordance with the same procedures as in Example 364, using (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine prepared in Example 375.

Example 385

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile prepared in Example 376.

Example 386

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine prepared in Example 374.

Example 387 <Step 1> tert-butyl 1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Example 1, using 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared in Preparation 3 and 3-(tert-butoxycarbonylamino)pyrrolidine.

<Step 2> 3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Example 47, using tert-butyl 1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate prepared in Step 1.

<Step 3> 3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Example 372, using 3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile dihydrochloride prepared in Step 2.

<Step 4> 3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile dihydrochloride

The titled compound in the form of white solid was prepared in accordance with the same procedures as in Example 118, using 3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Step 3.

Examples 388 to 392

The products of Examples 388 to 392 were prepared in accordance with the same procedures as in Example 1, using 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine prepared in Preparation 9; and L-prolinol, (3S)-(−)-3-acetamidopyrrolidine, (S)-2-(methoxymethyl)pyrrolidine, 2-methylpyrrolidine, or (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 393

A solution of (R)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile (30 mg, 0.09 mmol) prepared in Example 57, phenol (13.1 mg, 0.14 mmol), and cyanomethylenetributylphosphorane (37 μl, 0.14 mmol) in toluene (0.5 mol) was stirred in a microwave reactor (400 W) for 1 hour. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=100/1) to give 4.0 mg of the product as pale yellow oil.

Example 394

The product was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)acetamide prepared in Example 77.

Example 395

A catalytic amount of palladium/charcoal was added to a solution of (S)-benzyl 2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-2-oxoethylcarbamate (120 mg, 0.2 mmol) prepared in Example 165 in methanol (3 ml). The reaction mixture was stirred under hydrogen atmosphere at room temperature overnight. The reaction mixture was filtered through a celite pad. The resulting filtrate was concentrated under reduced pressure to give 21.2 mg of the product as colorless oil.

Example 396

The product was prepared in accordance with the same procedures as in Example 118, using (S)-3-(4-{3-[4-(dimethylamino)benzylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile prepared in Example 110.

Example 397

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-2-fluoro-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile prepared in Example 214.

Example 398

The product in the form of pale red solid was prepared in accordance with the same procedures as in Example 118, using (S)-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol prepared in Example 212.

Example 399

The product in the form of pale red solid was prepared in accordance with the same procedures as in Example 221, using (S)-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl]methanol prepared in Example 210.

Example 400

The product in the form of pale red solid was prepared in accordance with the same procedures as in Example 221, using (S)-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol prepared in Example 208.

Example 401

The product in the form of pale red solid was prepared in accordance with the same procedures as in Example 221, using (S)-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol prepared in Example 196.

Example 402

Dess-Martin periodinane (449 mg, 1.06 mmol) was added at room temperature to a solution of (S)-3-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile (238 mg, 0.71 mmol) prepared in Example 194 in dichloromethane (3.5 ml), and then stirred for 4 hours. Dess-Martin periodinane (449 mg, 1.06 mmol) was further added at room temperature to the reaction mixture, which was then stirred overnight. The reaction mixture was diluted with ethyl ether, washed with an aqueous saturated solution of sodium bicarbonate, dried on anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1) to give 154 mg of the product as pale yellow oil.

Example 403

A solution of (S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile (20 mg, 0.06 mmol) prepared in Example 402 and methylamine hydrochloride (4.8 mg, 0.07 mmol) in methanol (0.5 ml) was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (25.3 mg, 0.12 mmol) and acetic acid (5.1 μl, 0.09 mmol) were added to the reaction mixture, which was then stirred at room temperature overnight. An aqueous saturated solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was dried on anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/methanol=1/1) to give 7 mg of the product as colorless oil.

Examples 404 to 407

The products of Examples 404 to 407 were prepared in accordance with the same procedures as in Example 403, using (S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile prepared in Example 402; and cyclobutylamine hydrochloride, 4-fluorobenzylamine, n-propylamine, or ethanolamine.

Example 408

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using Example N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 294.

Example 409

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using N-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 295.

Example 410

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 297.

Example 411

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine prepared in Example 328.

Example 412

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine prepared in Example 323.

Example 413

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 118, using (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile prepared in Example 377.

Examples 414 to 421

The products of Examples 414 to 421 were prepared in accordance with the same procedures as in Example 84, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 354; and propionaldehyde, 3-(methylthio)propionaldehyde, pyrrole-2-carboxaldehyde, 4-hydroxybenzaldehyde, acetone, cyclobutanone, cyclopentanone, or cyclohexanone.

Example 422

A solution of (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride (20 mg, 0.05 mmol) prepared in Example 354 and pentanal (4.3 mg, 0.05 mmol) in methanol (1 ml) was stirred at room temperature for 30 minutes and then sodium cyanoborohydride (9.4 mg, 0.15 mmol) was added thereto. The reaction mixture was stirred at room temperature for 3 hours and then an aqueous saturated solution of sodium bicarbonate was added thereto to terminate the reaction. The reaction mixture was extracted with ethyl acetate. The resulting organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=1/1), and then dissolved in ethyl acetate (1 ml). Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 8 mg of the product as a white solid.

Examples 423 and 424

The products of Examples 423 and 424 were prepared in accordance with the same procedures as in Example 422, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 354; and pivaldehyde or 4,5-dimethylfuran-2-carboxaldehyde.

Examples 425 to 430

The products of Examples 425 to 430 were prepared in accordance with the same procedures as in Example 61, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 354; and propionic acid, 2-phenylacetic acid, 2-(piperidin-1-yl)acetic acid, 2-(pyridin-3-yl)acetic acid, 2-(pyridin-4-yl)acetic acid, or 2-(thiophene-2-yl)acetic acid.

Example 431

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 124, using (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride prepared in Example 354 and methanesulfonyl chloride.

Example 432

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamide prepared in Example 431.

Example 433

Ethyl isocyanate (7.1 mg, 0.1 mmol) was slowly added at room temperature to a solution of (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile dihydrochloride (20 mg, 0.05 mmol) prepared in Example 354 and diisopropylethylamine (0.03 ml, 0.14 mmol) in dichloromethane (1 ml). The reaction mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, which was then extracted with dichloromethane. The separated organic layer was dried on anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate) and then dissolved in ethyl acetate (2 ml). Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 2 hours and then filtered to give 6 mg of the product as a white solid.

Example 434

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 84, using (R)-3-{4-[3-(aminomethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile dihydrochloride prepared in Example 179 and acetaldehyde.

Example 435

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)-5-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile prepared in Example 418.

Examples 436 to 446

The products of Examples 436 to 446 were prepared in accordance with the same procedures as in Example 26, using (S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamide prepared in Preparation 24; and 4-methyl-3-nitroaniline, 4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline, 3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine, 2-(trifluoromethyl)benzene-1,4-diamine, 4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile, 4-fluoro-1,3-phenylenediamine, 4-chloro-1,3-phenylenediamine, or 2,5-diaminobenzonitrile prepared in Preparation 19.

Example 447

A solution of (S)-tert-butyl 1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate (85 mg, 0.23 mmol) prepared in Preparation 25 and 2,5-diaminobenzonitrile (34 mg, 0.25 mmol) prepared in Preparation 19 in n-butanol (0.5 ml) was stirred at 130° C. for 3 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=20/1) and then dissolved in ethyl acetate/methanol (1 ml/1 ml). The resulting solution was saturated with hydrogen chloride gas and then filtered to give 46.7 mg of the product as a white solid.

Examples 448 to 457

The products of Examples 448 to 457 were prepared in accordance with the same procedures as in Example 447, using (S)-tert-butyl 1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate prepared in Preparation 25; and 4-methyl-3-nitroaniline, 4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline, 3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine, 2-(trifluoromethyl)benzene-1,4-diamine, 4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile, 4-fluoro-1,3-phenylenediamine, or 4-chloro-1,3-phenylenediamine.

Examples 458 to 471

The products of Examples 458 to 471 were prepared in accordance with the same procedures as in Example 447, using (S)-tert-butyl 1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate prepared in Preparation 26; and 2,5-diaminobenzonitrile prepared in Preparation 19, 3-aminobenzonitrile, 5-amino-2-methylbenzonitrile, 2-nitro-1,4-phenylenediamine, 4-methyl-3-nitroaniline, 4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline, 3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine, 2-(trifluoromethyl)benzene-1,4-diamine, 4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile, 4-fluoro-1,3-phenylenediamine, or 4-chloro-1,3-phenylenediamine.

Example 472

A mixture of (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide (20 mg, 0.07 mmol) prepared in Preparation 27 and 5-amino-2-methylbenzonitrile (10.6 mg, 0.08 mmol) in n-butanol (0.5 ml) was stirred in a microwave reactor (600 W) for 1 hour. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/methanol=20/1) to give 5.9 mg of the product as yellow oil.

Examples 473 to 481

The products of Examples 473 to 481 were prepared in accordance with the same procedures as in Example 472, using (S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide prepared in Preparation 27; and 5-amino-2-fluorobenzonitrile, 3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine, 2-(trifluoromethyl)benzene-1,4-diamine, 4-fluoro-3-trifluoromethylphenylamine, 4-fluoro-1,3-phenylenediamine, 4-chloro-1,3-phenylenediamine, 2-chloro-4-aminotoluene, or 4-methyl-3-(trifluoromethyl)aniline.

Example 482

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide prepared in Example 474.

Example 483

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide prepared in Example 472.

Example 484

A solution of (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate (0.2 g, 0.56 mmol) prepared in Preparation 28, 4-fluorobenzene-1,3-diamine (0.1 g, 0.61 mmol), and diisopropylethylamine (0.2 ml, 1.12 mmol) in n-butanol (2 ml) was stirred at 130° C. overnight. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (dichloromethane/ethyl acetate=20/1) and then dissolved in ethyl acetate (2 ml). Hydrogen chloride gas was added to the solution. The reaction mixture was stirred at room temperature for 1 hour and then filtered to give 0.1 g of the product as a white solid.

Examples 485 to 487

The products of Examples 485 to 487 were prepared in accordance with the same procedures as in Example 484, using (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate prepared in Preparation 28; and 3,5-diaminobenzonitrile, 2,5-diaminobenzonitrile prepared in Preparation 19, or 5-(trifluoromethyl)-1,3-phenylenediamine.

Examples 488 to 489

The products of Examples 488 to 489 was prepared in accordance with the same procedures as in Example 484, using (S)-tert-butyl 1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate prepared in Preparation 29; and 2-(trifluoromethyl)-1,4-phenylenediamine or 2,5-diaminobenzonitrile prepared in Preparation 19.

Examples 490 and 491

The products of Examples 490 and 491 were prepared in accordance with the same procedures as in Example 172, using 4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine prepared in Preparation 30; and (3S)-(−)-3-(methylamino)pyrrolidine or (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 492

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 228.

Example 493

The product in the form of white solid was prepared in accordance with the same procedures as in Example 118, using (S)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide prepared in Example 292.

Example 494

The product in the form of pale yellow solid was prepared in accordance with the same procedures as in Example 395, using (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide hydrochloride prepared in Example 286.

The compounds of Examples 1 to 494 and the NMR spectrum data thereof are shown in Tables 1-1 to 1-51 below.

TABLE 1-1 Example Compound NMR Spectrum 1 N-(4-fluorophenyl)-4-propyl- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H), 6.97(t, 6-(pyrrolidin-1-yl)pyrimidin- 2H), 5.68(s, 1H), 3.70-3.20(m, 4H), 2.46(t, 2H), 2.10- 2-amine 1.90(m, 4H), 1.80-1.60(m, 2H), 0.97(t, 3H) 2 (S)-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.99(t, fluorophenylamino)-6- 2H), 6.75(brs, 1H), 5.74(s, 1H), 4.38(brs, 1H), 3.80- propylpyrimidin-4- 3.60(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m, 1H), 2.48(t, yl]pyrrolidin-2-yl}methanol 2H), 2.10-1.90(m, 3H), 1.80-1.60(m, 3H), 0.98(t, 3H) 3 1-[2-(4-fluorophenylamino)- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.97(t, 6-propylpyrimidin-4- 2H), 6.84(brs, 1H), 5.70(s, 1H), 4.62(brs, 1H), 3.63(brs, yl]pyrrolidin-3-ol 4H), 2.46(t, 2H), 2.20-2.00(m, 2H), 1.71(q, 2H), 0.98(t, 3H) 4 (R)-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.45(m, 2H), 6.98(t, fluorophenylamino)-6- 2H), 6.83(brs, 1H), 5.74(s, 1H), 4.35(brs, 1H), 3.70- propylpyrimidin-4- 3.55(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m, 1H), 2.47(t, yl]pyrrolidin-2-yl}methanol 2H), 2.10-1.90(m, 3H), 1.80-1.60(m, 3H), 0.98(t, 3H) 5 {1-[2-(4-fluorophenylamino)- ¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.45(m, 2H), 6.98(t, 6-propylpyrimidin-4- 2H), 6.83(brs, 1H), 5.74(s, 1H), 4.35(brs, 1H), 3.70- yl]pyrrolidin-2-yl}methanol 3.55(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m, 1H), 2.47(t, 2H), 2.10-1.90(m, 3H), 1.80-1.60(m, 3H), 0.98(t, 3H) 6 N-(4-fluorophenyl)-4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, methylpyrrolidin-1-yl)-6- 2H), 6.83(brs, 1H), 5.68(s, 1H), 4.20(brs, 1H), 3.55(brs, propylpyrimidin-2-amine 1H), 3.38(brs, 1H), 2.45(t, 2H), 2.10-1.90(m, 3H), 1.80- 1.65(m, 3H), 1.23(d, 3H), 0.98(t, 3H) 7 (S)-N-(4-fluorophenyl)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, (methoxymethyl)pyrrolidin- 2H), 6.86(brs, 1H), 5.73(s, 1H), 4.30-4.10(brs, 1H), 1-yl]-6-propylpyrimidin-2- 3.66(brs, 1H), 3.49(brs, 1H), 3.36(s, 3H), 3.30-3.15(m, amine 2H), 2.46(t, 2H), 2.10-1.85(m, 4H), 1.71(q, 2H), 0.98(t, 3H) 8 (R)-N-(4-fluorophenyl)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, (methoxymethyl)pyrrolidin- 2H), 6.86(brs, 1H), 5.73(s, 1H), 4.30-4.10(brs, 1H), 1-yl]-6-propylpyrimidin-2- 3.66(brs, 1H), 3.49(brs, 1H), 3.36(s, 3H), 3.30-3.15(m, amine 2H), 2.46(t, 2H), 2.10-1.85(m, 4H), 1.71(q, 2H), 0.98(t, 3H) 9 (S)-1-[2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.65-7.55(m, 2H), 6.97(t, fluorophenylamino)-6- 2H), 5.90(s, 1H), 4.60-4.40(m, 1H), 3.75-3.60(m, 1H), propylpyrimidin-4- 3.55-3.35(m, 1H), 2.47(t, 2H), 2.30-2.20(m, 1H), 2.15- yl]pyrrolidin-2-carboxamide 1.95(m, 3H), 1.72(q, 2H), 0.98(t, 3H) 10 N-{1-[2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.70-7.60(m, 2H), 6.98(t, fluorophenylamino)-6- 2H), 5.81(s, 1H), 4.44(t, 1H), 3.80-3.30(m, 4H), 2.45(t, propylpyrimidin-4- 2H), 2.30-2.20(m, 1H), 2.05-1.95(m, 1H), 1.94(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.71(q, 2H), 0.97(t, 3H)

TABLE 1-2 Example Compound NMR Spectrum 11 (R)-N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H), 6.98(t, fluorophenylamino)-6- 2H), 5.79(brs, 1H), 5.68(s, 1H), 4.65-4.55(m, 1H), 3.80- propylpyrimidin-4- 3.70(m, 1H), 3.65-3.45(m, 3H), 2.46(t, 2H), 2.00(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.80-1.60(m, 2H), 0.97(t, 3H) 12 2,2,2-trifluoro-N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.99(t, fluorophenylamino)-6- 2H), 6.80(brs, 1H), 6.54(brs, 1H), 5.70(s, 1H), 4.70- propylpyrimidin-4- 4.60(m, 1H), 3.85-3.75(m, 1H), 3.70-3.30(m, 3H), 2.48(t, yl]pyrrolidin-3-yl}acetamide 2H), 2.40-2.30(m, 1H), 2.15-2.05(m, 1H), 1.80-1.65(m, 2H), 0.98(t, 3H) 13 4-[3-(ethylamino)pyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.96(t, 1-yl]-N-(4-fluorophenyl)-6- 2H), 6.92(brs, 1H), 5.67(s, 1H), 3.47(t, 2H), 2.72(q, 2H), propylpyrimidin-2-amine 2.45(t, 2H), 2.25-2.10(m, 1H), 1.90-1.80(m, 1H), 1.71(q, 2H), 1.15(t, 3H), 0.99(t, 3H) 14 4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.96(t, (dimethylamino)pyrrolidin-1- 2H), 6.88(brs, 1H), 5.68(s, 1H), 4.00-3.50(m, 2H), 3.50- yl]-N-(4-fluorophenyl)-6- 3.30(m, 1H), 3.30-3.10(m, 1H), 2.85-2.70(m, 1H), 2.46(t, propylpyrimidin-2-amine 2H), 2.31(s, 6H), 2.20-2.10(m, 1H), 1.90-1.80(m, 1H), 1.72(q, 2H), 0.97(t, 3H) 15 (S)-N-(4-fluorophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H), 6.97(t, propyl-6-[2-(pyrrolidin-1- 2H), 5.72(s, 1H), 3.60-3.20(m, 2H), 3.10-2.60(m, 6H), ylmethyl)pyrrolidin-1- 2.51(t, 2H), 2.40-2.20(m, 1H), 2.10-2.00(m, 4H), 2.00- yl]pyrimidin-2-amine 1.80(m, 4H), 1.75(q, 2H), 0.99(t, 3H) 16 (S)-N-(4-fluorophenyl)-4-{2- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 7.20- [(phenylamino)methyl]pyrrolidin- 7.10(m, 2H), 6.93(t, 2H), 6.79(brs, 1H), 6.65(t, 1H), 6.50- 1-yl}-6-propylpyrimidin- 6.40(m, 2H), 5.72(s, 1H), 4.70-4.40(m, 1H), 3.60-3.20(m, 2-amine 3H), 3.20-3.10(m, 1H), 2.46(t, 2H), 2.20-1.90(m, 4H), 1.71(q, 2H), 0.98(t, 3H) 17 (S)-N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 7.05- fluorophenylamino)-6- 6.90(m, 3H), 6.08(brs, 1H), 5.66(s, 1H), 4.56(brs, 1H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.45(t, 2H), 2.30-2.15(m, 1H), 1.98(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.00-1.90(m, 1H), 1.70(q, 2H), 0.96(t, 3H) 18 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.96(t, (ethylamino)pyrrolidin-1-yl]- 2H), 6.92(brs, 1H), 5.67(s, 1H), 3.47(t, 2H), 2.72(q, 2H), N-(4-fluorophenyl)-6- 2.45(t, 2H), 2.25-2.10(m, 1H), 1.90-1.80(m, 1H), 1.71(q, propylpyrimidin-2-amine 2H), 1.14(t, 3H), 0.97(t, 3H) 19 (S)-tert-butyl 1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, fluorophenylamino)-6- 2H), 6.86(brs, 1H), 5.68(s, 1H), 4.72(brs, 1H), 4.34(brs, propylpyrimidin-4- 1H), 3.80-3.20(m, 4H), 2.46(t, 2H), 2.30-2.20(m, 1H), yl]pyrrolidin-3-ylcarbamate 2.05-1.90(m, 1H), 1.71(q, 2H), 1.46(s, 9H), 0.97(t, 3H) 20 4-(3-aminopyrrolidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.70-7.60(m, 2H), 6.98(t, N-(4-fluorophenyl)-6- 2H), 5.84(s, 1H), 3.90-3.35(m, 5H), 2.46(t, 2H), 2.35- propylpyrimidin-2-amine 2.25(m, 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-3 Example Compound NMR Spectrum 21 4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 7.05- (diethylamino)pyrrolidin-1- 6.90(m, 3H), 5.68(s, 1H), 4.00-3.10(m, 5H), 2.80-2.60(m, yl]-N-(4-fluorophenyl)-6- 4H), 2.46(t, 2H), 2.25-2.15(m, 1H), 1.90-1.80(m, 1H), propylpyrimidin-2-amine 1.72(q, 2H), 1.06(t, 6H), 0.98(t, 3H) 22 (S)-N-(4-fluorophenyl)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H), 7.20(brs, (methylamino)pyrrolidin-1- 1H), 6.97(t, 2H), 5.68(s, 1H), 3.80-3.10(m, 5H), 2.49(s, yl]-6-propylpyrimidin-2- 3H), 2.47(t, 2H), 2.20-2.10(m, 1H), 1.90-1.80(m, 1H), amine 1.71(q, 2H), 0.98(t, 3H) 23 N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.98(t, fluorophenylamino)-6- 2H), 6.88(brs, 1H), 5.69(s, 1H), 5.39(t, 1H), 3.80-3.20(m, propylpyrimidin-4- 4H), 2.94(s, 3H), 2.47(t, 2H), 2.30-2.20(m, 2H), 2.14(s, yl]pyrrolidin-3-yl}-N- 3H), 1.72(q, 2H), 0.98(t, 3H) methylacetamide 24 (S)-1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, fluorophenylamino)-6- 2H), 6.85(brs, 1H), 5.68(s, 1H), 4.62(brs, 1H), 3.80- propylpyrimidin-4- 3.30(m, 4H), 2.46(t, 2H), 2.20-2.00(m, 2H), 1.71(q, 2H), yl]pyrrolidin-3-ol 0.97(t, 3H) 25 4-[3-(ethylamino)pyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 7.65-7.55(m, 2H), 7.17(t, 1-yl]-N-(4-fluorophenyl)-6- 2H), 6.28(s, 1H), 4.20-4.00(m, 2H), 4.00-3.80(m, 2H), propylpyrimidin-2-amine 3.80-3.70(m, 1H), 3.25-3.10(m, 2H), 2.68(t, 2H), 2.60- dihydrochloride 2.45(m, 1H), 2.40-2.20(m, 1H), 1.79(t, 2H), 1.45-1.30(m, 3H), 1.07(t, 3H) 26 (S)-N-{4-[2- ¹H-NMR(400 MHz, CD₃OD) δ 7.61(s, 1H), 7.55(d, 1H), (methoxymethyl)pyrrolidin- 7.26(s, 1H), 7.04(d, 1H), 6.45(s, 1H), 6.10(s, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 4.43(brs, 1H), 3.60(brs, 1H), 3.48(brs, 1H), 3.50-3.40(m, 1H-indol-6-amine 2H), 3.10(s, 3H), 2.59(t, 2H), 2.25-1.95(m, 4H), 1.74(q, hydrochloride 2H), 1.04(t, 3H) 27 (S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.10-8.00(m, 2H), 7.35- (methoxymethyl)pyrrolidin- 7.25(m, 1H), 7.17(s, 1H), 6.90-6.80(m, 1H), 6.49(s, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(brs, 1H), 3.80-3.60(m, 2H), 3.60-3.40(m, 2H), 1H-indol-5-amine 3.33(s, 3H), 3.30-3.20(m, 1H), 2.46(t, 2H), 2.10-1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) 28 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.90- (methoxymethyl)pyrrolidin- 6.80(m, 2H), 6.74(brs, 1H), 5.70(s, 1H), 4.35(brs, 1H), 1-yl]-N-(4-methoxyphenyl)- 3.79(s, 3H), 3.80-3.60(m, 1H), 3.50-3.40(m, 1H), 3.36(s, 6-propylpyrimidin-2-amine 3H), 3.30-3.20(m, 2H), 2.50-2.40(m, 2H), 2.20-1.90(m, 4H), 1.80-1.65(m, 2H), 1.00-0.90(m, 3H) 29 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 1H), 7.20- (methoxymethyl)pyrrolidin- 7.10(m, 2H), 6.87(brs, 1H), 6.51(d, 1H), 5.74(s, 1H), 1-yl]-N-(3-methoxyphenyl)- 3.81(s, 3H), 3.80-3.60(m, 2H), 3.60-3.40(m, 1H), 3.36(s, 6-propylpyrimidin-2-amine 3H), 3.30-3.20(m, 2H), 2.46(t, 2H), 2.10-1.90(m, 4H), 1.72(q, 2H), 0.98(t, 3H) 30 (S)-N-(3-chlorophenyl)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.95(s, 1H), 7.34(d, 1H), (methoxymethyl)pyrrolidin- 7.17(t, 1H), 7.00-6.80(m, 2H), 5.76(brs, 1H), 4.50- 1-yl]-6-propylpyrimidin-2- 4.30(m, 1H), 3.80-3.30(m, 4H), 3.37(s, 3H), 2.47(t, 2H), amine 2.20-1.90(m, 4H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-4 Example Compound NMR Spectrum 31 (S)-N-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.00-8.70(m, 1H), 7.70- nitrophenyl)-4-[2- 7.40(m, 1H), 7.16(t, 1H), 7.11(brs, 1H), 5.83(brs, 1H), (methoxymethyl)pyrrolidin- 4.50-4.20(m, 1H), 3.70-3.35(m, 4H), 3.36(s, 3H), 2.48(t, 1-yl]-6-propylpyrimidin-2- 2H), 2.20-1.90(m, 4H), 1.72(q, 2H), 0.98(t, 3H) amine 32 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.75(brs, 1H), 7.48(brs, 2H), (methoxymethyl)pyrrolidin- 7.37(d, 1H), 6.05(brs, 1H), 5.83(brs, 1H), 4.40(brs, 1H), 1-yl]-N-(3-nitrophenyl)-6- 3.65-3.40(m, 4H), 3.36(s, 3H), 2.60-2.40(m, 2H), 2.30- propylpyrimidin-2-amine 1.90(m, 4H), 1.71(q, 2H), 0.98(t, 3H) 33 (S)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 7.77(dd, 1H), 7.64(brs, 1H), nitrophenyl)-4-[2- 7.38(t, 1H), 7.19(brs, 1H), 5.83(brs, 1H), 4.60-4.30(m, (methoxymethyl)pyrrolidin- 1H), 3.70-3.40(m, 4H), 3.36(s, 3H), 2.49(t, 2H), 2.20- 1-yl]-6-propylpyrimidin-2- 1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) amine 34 (S)-3-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.23(brs, 1H), 7.66(brs, 1H), (methoxymethyl)pyrrolidin- 7.34(t, 1H), 7.21(d, 1H), 7.08(brs, 1H), 5.81(brs, 1H), 1-yl]-6-propylpyrimidin-2- 4.50-4.30(m, 1H), 3.70-3.40(m, 4H), 3.31(s, 3H), 2.48(t, ylamino}benzonitrile 2H), 2.20-1.90(m, 4H), 1.72(q, 2H), 0.99(t, 3H) 35 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.66(br, 1H), 7.40(br, 1H), (methoxymethyl)pyrrolidin- 7.19(t, 2H), 6.85(d, 1H), 5.75(br, 1H), 4.37(br, 1H), 1-yl]-N-[3- 3.63(br, 2H), 3.36(s, 3H), 2.48(m, 5H), 2.09(m, 2H), (methylthio)phenyl]-6- 2.00(m, 2H), 1.74(m, 2H), 0.98(t, 3H) propylpyrimidin-2-amine 36 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.89(br, 1H), 8.45-8.20(br, (methoxymethyl)pyrrolidin- 1H), 7.65(br, 1H), 7.39(t, 1H), 7.25(m, 1H), 5.78-5.62(br, 1-yl]-6-propyl-N-[3- 2H), 4.49-4.05(br, 1H), 3.54(br, 3H), 3.33(br, 4H), 2.55(t, (trifluoromethyl)phenyl]pyrimidin- 2H), 2.04(br, 2H), 1.81(m, 2H), 1.00(t, 3H) 2-amine 37 (S)-7-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.03(br, 1H), 7.69(br, 1H), (methoxymethyl)pyrrolidin- 7.46(d, 1H), 7.35(br, 1H), 6.12(s, 1H), 5.80(br, 1H), 4.53- 1-yl]-6-propylpyrimidin-2- 3.73(br, 2H), 3.57-3.22(br, 2H), 3.40(s, 3H), 2.73(br, 1H), ylamino}-4-methyl-2H- 2.50(t, 2H), 2.39(s, 3H), 2.18(m, 1H), 2.05(m, 3H), chromen-2-one 1.76(m, 2H), 0.97(t, 3H) 38 (S)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.24(br, 1H), 8.05(br, 1H), methylphenyl)-4-[2- 6.95(d, 1H), 6.93(d, 1H), 5.76(br, 1H), 4.44(br, 1H), (methoxymethyl)pyrrolidin- 3.53(br, 3H), 3.31(br, 4H), 2.55(t, 2H), 2.40(s, 3H), 2.10- 1-yl]-6-propylpyrimidin-2- 2.01(m, 4H), 1.79(m, 2H), 1.01(t, 3H) amine 39 (S)-N-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.56(br, 1H), 7.89(br, 1H), methylphenyl)-4-[2- 7.30(m, 1H), 7.11(d, 1H), 5.89-5.73(br, 2H), 3.63- (methoxymethyl)pyrrolidin- 3.48(br, 3H), 3.35(m, 4H), 2.53(t, 2H), 2.30(s, 3H), 2.10- 1-yl]-6-propylpyrimidin-2- 2.03(m, 4H), 1.79(m, 2H), 1.00(t, 3H) amine 40 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 9.00-8.73(br, 2H), 7.52(br, (methoxymethyl)pyrrolidin- 1H), 7.22(d, 1H), 5.96(br, 1H), 5.55(br, 1H), 4.55- 1-yl]-N-(4-methyl-3- 4.10(br, 1H), 3.59(br, 3H), 3.33(m, 4H), 2.55(m, 4H), nitrophenyl)-6- 2.60(m, 4H), 1.79(m, 2H), 1.00(t, 3H) propylpyrimidin-2-amine

TABLE 1-5 Example Compound NMR Spectrum 41 (S)-N-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.20(br, 1H), 8.42-8.12(br, (trifluoromethyl)phenyl]-4- 1H), 7.67(br, 1H), 7.12(t, 1H), 5.78(br, 2H), 4.45-4.07(br, [2- 1H), 3.50(br, 3H), 3.32(m, 4H), 2.56(t, 2H), 2.06(m, 4H), (methoxymethyl)pyrrolidin- 1.81(m, 2H), 1.00(t, 3H) 1-yl]-6-propylpyrimidin-2- amine 42 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.93(br, 1H), 7.41(br, 1H), (methoxymethyl)pyrrolidin- 6.76(br, 1H), 6.69(d, 1H), 5.72(br, 1H), 4.36(br, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 4.00(s, 2H), 3.55(br, 2H), 3.33(m, 5H), 2.45(t, 2H), 3-(trifluoromethyl)benzene- 2.09(m, 2H), 2.00(m, 2H), 1.72(m, 2H), 0.97(t, 3H) 1,4-diamine 43 (S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.21(br, 1H), 8.06(br, 1H), (methoxymethyl)pyrrolidin- 7.11(t, 1H), 5.80(br, 1H), 4.45(br, 1H), 3.62(m, 3H), 1-yl]-6-propylpyrimidin-2- 3.37(m, 5H), 2.51(t, 2H), 2.12-2.04(m, 4H), 1.75(m, 2H), ylamino}benzonitrile 0.99(t, 3H) 44 (S)-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.58(br, 1H), 8.17(br, 1H), (methoxymethyl)pyrrolidin- 7.57(br, 1H), 7.22(d, 1H), 5.78(br, 1H), 5.31(br, 1H), 1-yl]-6-propylpyrimidin-2- 4.49-4.00(br, 1H), 3.63(m, 3H), 3.41(m, 4H), 2.55(t, 2H), ylamino}-2- 2.51(s, 3H), 2.18-2.05(m, 4H), 1.77(m, 2H), 0.99(t, 3H) methylbenzonitrile 45 (S)-2-amino-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.92(br, 1H), 7.43(m, 1H), (methoxymethyl)pyrrolidin- 7.12(br, 1H), 6.71(d, 1H), 5.75(br, 1H), 4.40(br, 1H), 1-yl]-6-propylpyrimidin-2- 4.19(s, 2H), 3.53(br, 3H), 3.36(s, 5H), 2.47(t, 2H), ylamino}benzonitrile 2.21(br, 2H), 2.05(m, 2H), 1.97(m, 2H), 1.72(m, 2H), 0.98(t, 3H) 46 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.72(br, 1H), 8.35(br, 1H), (methoxymethyl)pyrrolidin- 7.41(br, 1H), 6.80(d, 1H), 6.06(s, 2H), 5.78(br, 1H), 4.60- 1-yl]-6-propylpyrimidin-2-yl}- 4.10(br, 3H), 3.54(br, 3H), 3.32(m, 3H), 2.52(t, 2H), 2.18- 3-nitrobenzene-1,4-diamine 2.03(m, 2H), 1.79(m, 2H), 0.99(t, 3H) 47 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.60-7.45(m, 2H), 7.15(t, yl)-N-(4-fluorophenyl)-6- 2H), 6.30-6.20(m, 1H), 4.10-3.91(m, 2H), 3.90-3.70(m, propylpyrimidin-2-amine 3H), 2.66(t, 2H), 2.60-2.40(m, 1H), 2.30-2.10(m, 1H), dihydrochloride 1.80-1.65(m, 2H), 1.05(t, 3H) 48 (S)-tert-butyl 1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.62(brs, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.21(d, 1H), 7.01(brs, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.71(brs, 1H), 4.34(brs, 1H), 3.80-3.20(m, 4H), 2.48(t, yl]pyrrolidin-3-ylcarbamate 2H), 2.40-2.20(m, 1H), 2.10-1.90(m, 1H), 1.72(q, 2H), 1.46(s, 9H), 0.98(t, 3H) 49 3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(brs, 1H), 7.55(d, 1H), (diethylamino)pyrrolidin-1- 7.32(t, 1H), 7.20(d, 1H), 7.13(brs, 1H), 5.74(s, 1H), 4.00- yl]-6-propylpyrimidin-2- 3.80(m, 1H), 3.70-3.10(m, 4H), 2.71(d, 4H), 2.48(t, 2H), ylamino}benzonitrile 2.25-2.15(m, 1H), 2.00-1.85(m, 1H), 1.72(q, 2H), 1.05(t, 6H), 0.98(t, 3H) 50 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.57(dd, 1H), (methylamino)pyrrolidin-1- 7.32(t, 1H), 7.19(d, 1H), 7.17(brs, 1H), 5.74(s, 1H), 3.90- yl]-6-propylpyrimidin-2- 3.10(m, 5H), 2.50(s, 3H), 2.48(t, 2H), 2.30-2.10(m, 1H), ylamino}benzonitrile 1.90-1.85(m, 1H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-6 Example Compound NMR Spectrum 51 N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.61(d, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.21(d, 1H), 7.02(s, 1H), 5.75(s, 1H), 5.37(t, propylpyrimidin-4- 1H), 3.90-3.20(m, 4H), 2.96(s, 3H), 2.49(t, 2H), 2.30- yl]pyrrolidin-3-yl}-N- 2.20(m, 2H), 2.15(s, 3H), 1.73(q, 2H), 0.98(t, 3H) methylacetamide 52 (S)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.55(dd, 1H), hydroxypyrrolidin-1-yl)-6- 7.32(t, 1H), 7.20(d, 1H), 7.00(brs, 1H), 5.75(s, 1H), propylpyrimidin-2- 4.65(brs, 1H), 3.90-3.30(m, 4H), 2.48(t, 2H), 2.20- ylamino]benzonitrile 2.00(m, 2H), 1.72(q, 2H), 0.98(t, 3H) 53 (R)-3-[4-(2-methylpyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.46(brs, 1H), 7.52(d, 1H), 1-yl)-6-propylpyrimidin-2- 7.40-7.25(m, 2H), 7.18(d, 1H), 5.75(s, 1H), 4.50-4.10(m, ylamino]benzonitrile 1H), 3.70-3.20(m, 2H), 2.47(t, 2H), 2.20-1.90(m, 3H), 1.80-1.60(m, 3H), 1.30-1.20(m, 3H), 0.97(t, 3H) 54 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.60(brs, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.20(d, 1H), 7.06(brs, 1H), 5.80(d, 1H), propylpyrimidin-4- 5.75(s, 1H), 4.60(q, 1H), 3.90-3.20(m, 4H), 2.48(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.40-2.25(m, 1H), 2.01(s, 3H), 1.83(brs, 1H), 1.72(q, 2H), 0.98(t, 3H) 55 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H), (ethylamino)pyrrolidin-1-yl]- 7.32(t, 1H), 7.19(d, 1H), 7.15(brs, 1H), 5.74(s, 1H), 3.90- 6-propylpyrimidin-2- 3.10(m, 5H), 2.74(q, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), ylamino}benzonitrile 1.90-1.80(m, 1H), 1.72(q, 2H), 1.15(t, 3H), 0.98(t, 3H) 56 (R)-tert-butyl {1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.60(d, 1H), cyanophenylamino)-6- 7.37(brs, 1H), 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H), propylpyrimidin-4- 4.75(brs, 1H), 3.90-3.00(m, 6H), 2.53(brs, 1H), 2.48(t, yl]pyrrolidin-3- 2H), 2.20-2.10(m, 1H), 1.78(brs, 1H), 1.72(q, 2H), yl}methylcarbamate 1.46(s, 9H), 0.98(t, 3H) 57 (R)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.82(d, 1H), hydroxypyrrolidin-1-yl)-6- 7.39(t, 1H), 7.21(d, 1H), 5.89(s, 1H), 4.55(s, 1H), propylpyrimidin-2- 3.62(brs, 4H), 2.51(t, 2H), 2.13(m, 2H), 1.73(m, 2H), ylamino]benzonitrile 0.97(t, 3H) 58 (S)-3-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.41(s, 1H), 7.80(d, 1H), methoxypyrrolidin-1-yl)-6- 7.39(t, 1H), 7.21(d, 1H), 5.89(s, 1H), 4.14(s, 1H), 3.60- propylpyrimidin-2- 3.55(m, 4H), 3.48(s, 3H), 2.49(t, 2H), 2.19-2.11(m, 2H), ylamino]benzonitrile 1.75(m, 2H), 0.98(t, 3H) 59 3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.10(m, 1H), 7.90- (methylamino)pyrrolidin-1- 7.80(m, 1H), 7.60-7.50(m, 2H), 6.35(s, 1H), 4.20-3.70(m, yl]-6-propylpyrimidin-2- 5H), 2.81(s, 3H), 2.69(t, 2H), 2.60-2.45(m, 1H), 2.45- ylamino}benzonitrile 2.25(m, 1H), 1.80(q, 2H), 1.06(t, 3H) dihydrochloride 60 (S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.09(d, 1H), 7.90-7.80(m, 1-yl)-6-propylpyrimidin-2- 1H), 7.60-7.50(m, 2H), 6.40-6.30(m, 1H), 4.20-3.70(m, ylamino]benzonitrile 5H), 2.69(t, 2H), 2.60-2.45(m, 1H), 2.30-2.15(m, 1H), dihydrochloride 1.80(q, 2H), 1.06(t, 3H)

TABLE 1-7 Example Compound NMR Spectrum 61 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.60(brs, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.20(d, 1H), 7.04(brs, 1H), 5.75(s, 1H), propylpyrimidin-4- 5.70(d, 1H), 4.61(q, 1H), 3.80-3.20(m, 4H), 2.48(t, 2H), yl]pyrrolidin-3-yl}butyramide 2.40-2.25(m, 1H), 2.17(t, 2H), 2.05-1.95(m, 1H), 1.80- 1.60(m, 4H), 1.00-0.90(m, 6H) 62 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.60(brs, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.20(d, 1H), 7.09(brs, 1H), 5.75(s, 1H), propylpyrimidin-4- 5.71(d, 1H), 4.65-4.55(m, 1H), 3.90-3.15(m, 4H), 2.50- yl]pyrrolidin-3- 2.40(m, 3H), 2.35-2.25(m, 1H), 1.90-1.65(m, 9H), 1.60- yl}cyclopentanecarboxamide 1.50(m, 2H), 1.00(t, 3H) 63 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.53(brs, 1H), 8.38(brs, 1H), cyanophenylamino)-6- 7.62(brs, 1H), 7.34(t, 1H), 7.21(d, 1H), 7.02(brs, 1H), propylpyrimidin-4- 5.77(s, 1H), 4.59(brs, 1H), 3.90-3.20(m, 4H), 2.65(d, yl]pyrrolidin-3-yl}-3- 1H), 2.60-2.15(m, 10H), 1.90-1.85(m, 1H), 1.72(q, 2H), (piperidin-1-yl)propanamide 1.50-1.25(m, 6H), 0.99(t, 3H) 64 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(brs, 1H), 8.16(d, 1H), cyanophenylamino)-6- 7.79(d, 1H), 7.72(brs, 1H), 7.60-7.30(m, 5H), 7.22(d, propylpyrimidin-4- 1H), 6.55(brs, 1H), 5.75(s, 1H), 4.80(q, 1H), 4.00- yl]pyrrolidin-3-yl}benzamide 3.30(m, 4H), 2.53(t, 2H), 2.45-2.35(m, 1H), 2.25-2.15(m, 1H), 1.73(q, 2H), 1.00(t, 3H) 65 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.85-8.75(m, 2H), 8.31(brs, cyanophenylamino)-6- 1H), 7.60(brs, 1H), 7.33(t, 1H), 7.19(d, 1H), 7.15-7.00(m, propylpyrimidin-4- 3H), 6.40(brs, 1H), 5.77(s, 1H), 4.78(q, 1H), 4.00- yl]pyrrolidin-3-yl}-4- 3.30(m, 4H), 2.48(t, 2H), 2.40-2.30(m, 1H), 2.20-2.10(m, fluorobenzamide 1H), 1.72(q, 2H), 0.98(t, 3H) 66 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.28(brs, 1H), 7.59(d, 1H), cyanophenylamino)-6- 7.48(brs, 1H), 7.40-7.20(m, 7H), 5.69(s, 1H), 5.66(d, propylpyrimidin-4- 1H), 4.57(q, 1H), 3.58(s, 2H), 3.85-3.10(m, 4H), 2.47(t, yl]pyrrolidin-3-yl}-2- 2H), 2.30-2.20(m, 1H), 1.90-1.80(m, 1H), 1.70(q, 2H), phenylacetamide 0.97(t, 3H) 67 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.57(d, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.30-7.20(m, 4H), 7.09(brs, 1H), 7.02(t, 2H), propylpyrimidin-4- 5.72(s, 1H), 4.58(q, 1H), 3.53(s, 2H), 3.90-3.20(m, 4H), yl]pyrrolidin-3-yl}-2-(4- 2.48(t, 2H), 2.30-2.20(m, 1H), 1.90-1.85(m, 1H), 1.71(q, fluorophenyl)acetamide 1H), 0.97(t, 3H) 68 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, 1H), 7.90-7.80(m, cyanophenylamino)-6- 2H), 7.61(d, 1H), 7.33(t, 1H), 7.30-7.20(m, 3H), 7.00(brs, propylpyrimidin-4- 1H), 6.94(t, 1H), 6.22(d, 1H), 5.74(s, 1H), 4.62(q, 1H), yl]pyrrolidin-3-yl}-3- 4.26(t, 2H), 3.90-3.20(m, 4H), 2.67(t, 2H), 2.49(t, 2H), phenoxypropanamide 2.35-2.25(m, 1H), 1.80-1.60(m, 3H), 0.98(t, 3H) 69 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.02(s, 1H), 7.76(brs, 1H), cyanophenylamino)-6- 7.36(t, 1H), 7.30-7.20(m, 1H), 6.89(brs, 1H), 5.70(s, 1H), propylpyrimidin-4- 4.60(brs, 1H), 3.90-3.70(m, 3H), 3.65(t, 2H), 3.25- yl]pyrrolidin-3-yl}-3- 3.15(m, 3H), 2.63(t, 2H), 2.55-2.45(m, 3H), 2.40-2.30(m, isobutoxypropanamide 1H), 1.75-1.65(m, 1H), 0.99(t, 3H), 0.86(d, 6H) 70 (S)-2-(4-benzylpiperazin-1- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.65(brs, 1H), yl)-N-{1-[2-(3- 7.40-7.15(m, 8H), 5.75(s, 1H), 5.30(s, 1H), 4.65-4.55(m, cyanophenylamino)-6- 1H), 3.90-3.30(m, 4H), 3.02(s, 2H), 2.60-2.30(m, 11H), propylpyrimidin-4- 2.10-2.00(m, 1H), 1.72(q, 2H), 0.99(t, 3H) yl]pyrrolidin-3-yl}acetamide

TABLE 1-8 Example Compound NMR Spectrum 71 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(brs, 1H), 7.68(brs, 1H), cyanophenylamino)-6- 7.48(d, 1H), 7.36(t, 1H), 7.24(d, 1H), 5.75(s, 1H), 4.60(q, propylpyrimidin-4- 1H), 3.90-3.30(m, 4H), 3.01(s, 2H), 2.60-2.25(m, 7H), yl]pyrrolidin-3-yl}-2- 2.10-2.00(m, 1H), 1.71(q, 2H), 1.65-1.40(m, 6H), 0.98(t, (piperidin-1-yl)acetamide 3H) 72 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(brs, 1H), 8.03(s, 1H), cyanophenylamino)-6- 7.98(d, 2H), 7.90-7.85(m, 1H), 7.80(brs, 1H), 7.58(t, 1H), propylpyrimidin-4- 7.50-7.40(m, 3H), 7.33(t, 1H), 7.22(d, 1H), 7.12(brs, 1H), yl]pyrrolidin-3-yl}-4-oxo-4- 5.64(s, 1H), 4.63(brs, 1H), 3.90-3.20(m, 6H), 2.80- phenylbutanamide 2.60(m, 2H), 2.49(t, 2H), 2.30-2.20(m, 1H), 2.10-2.00(m, 1H), 1.67(q, 2H), 0.96(t, 3H) 73 (S)-2-(4-aminophenyl)-N-{1- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(brs, 1H), 7.60(brs, 1H), [2-(3-cyanophenylamino)-6- 7.34(t, 1H), 7.22(d, 1H), 7.02(d, 2H), 6.66(d, 2H), 5.70(s, propylpyrimidin-4- 1H), 5.55(d, 1H), 4.56(q, 1H), 3.90-3.50(m, 3H), 3.48(s, yl]pyrrolidin-3-yl}acetamide 2H), 3.30-3.10(m, 1H), 2.48(d, 2H), 2.30-2.20(m, 1H), 2.00-1.90(m, 1H), 1.71(q, 2H), 0.98(t, 3H) 74 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.33(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.21(d, 1H), 5.75(s, 1H), 5.63(brs, 1H), 4.65- propylpyrimidin-4- 4.55(m, 1H), 3.90-3.20(m, 4H), 2.49(t, 2H), 2.30-2.10(m, yl]pyrrolidin-3-yl}-2- 3H), 2.00-1.90(m, 1H), 1.90-1.45(m, 9H), 1.20-1.05(m, cyclopentylacetamide 2H), 0.98(t, 3H) 75 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 8.02(s, 1H), cyanophenylamino)-6- 7.78(d, 1H), 7.42(t, 1H), 7.40-7.25(m, 2H), 6.70(brs, 1H), propylpyrimidin-4- 5.77(s, 1H), 4.70-4.60(m, 1H), 3.91(s, 2H), 3.90-3.40(m, yl]pyrrolidin-3-yl}-2- 4H), 3.42(s, 3H), 2.60(t, 2H), 2.40-2.30(m, 1H), 2.10- methoxyacetamide 2.00(m, 1H), 1.72(q, 2H), 1.00(t, 3H) 76 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(s, 1H), 8.40(brs, 1H), cyanophenylamino)-6- 8.05(brs, 1H), 7.80-7.60(m, 2H), 7.40-7.15(m, 5H), propylpyrimidin-4- 5.73(s, 1H), 4.60-4.50(m, 1H), 3.74(s, 2H), 3.90-3.20(m, yl]pyrrolidin-3-yl}-2-(pyridin- 4H), 2.55(t, 2H), 2.35-2.25(m, 1H), 2.10-2.00(m, 1H), 2-yl)acetamide 1.70(t, 2H), 0.98(t, 3H) 77 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.51(s, 2H), 8.32(brs, 1H), cyanophenylamino)-6- 7.71(t, 2H), 7.40-7.20(m, 4H), 6.45(brs, 1H), 5.70(s, 1H), propylpyrimidin-4- 4.65-4.55(m, 1H), 3.57(s, 2H), 3.90-3.30(m, 4H), 2.55(t, yl]pyrrolidin-3-yl}-2-(pyridin- 2H), 2.30-2.20(m, 1H), 2.10-2.00(m, 1H), 1.69(q, 2H), 3-yl)acetamide 0.98(t, 3H) 78 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.80(brs, 1H), 8.52(d, 2H), cyanophenylamino)-6- 8.30(s, 1H), 7.70-7.65(m, 1H), 7.40-7.20(m, 5H), propylpyrimidin-4- 6.63(brs, 1H), 5.68(s, 1H), 4.62(q, 1H), 3.56(s, 2H), yl]pyrrolidin-3-yl}-2-(pyridin- 3.90-3.30(m, 4H), 2.53(t, 2H), 2.35-2.25(m, 1H), 2.10- 4-yl)acetamide 2.00(m, 1H), 1.68(q, 2H), 0.97(t, 3H) 79 (S,E)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(brs, 1H), 7.60(brs, 1H), cyanophenylamino)-6- 7.40-7.00(m, 8H), 6.53(d, 1H), 6.35-6.25(m, 1H), propylpyrimidin-4- 5.91(brs, 1H), 5.73(s, 1H), 4.65-4.55(m, 1H), 3.90- yl]pyrrolidin-3-yl}-4- 3.25(m, 4H), 3.17(d, 2H), 2.47(t, 2H), 2.35-2.25(m, 1H), phenylbut-3-enamide 2.00-1.80(m, 2H), 1.71(q, 2H), 0.98(t, 3H) 80 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.40-7.10(m, 4H), 7.00-6.85(m, 2H), 5.84(s, 1H), 5.69(s, propylpyrimidin-4- 1H), 4.60-4.50(m, 1H), 3.79(s, 2H), 3.80-3.20(m, 4H), yl]pyrrolidin-3-yl}-2- 2.49(t, 2H), 2.30-2.20(m, 1H), 2.00-1.85(m, 1H), 1.80- (thiophen-2-yl)acetamide 1.60(m, 2H), 1.00-0.90(m, 3H)

TABLE 1-9 Example Compound NMR Spectrum 81 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.35(t, 1H), 7.22(d, 1H), 5.75(s, 1H), 5.67(d, 1H), 4.60(q, propylpyrimidin-4- 1H), 3.90-3.20(m, 4H), 2.49(t, 2H), 2.20-1.90(m, 2H), yl]pyrrolidin-3- 1.17(d, 6H), 0.98(t, 3H) yljisobutyramide 82 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, 1H), 7.64(d, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.22(d, 1H), 6.43(d, 1H), 5.73(s, 1H), 4.64(q, propylpyrimidin-4- 1H), 4.00-3.30(m, 4H), 3.20-3.00(m, 2H), 2.51(t, 2H), yl]pyrrolidin-3-yl}-3,3,3- 2.40-2.30(m, 1H), 2.15-2.05(m, 1H), 1.71(q, 2H), 0.99(t, trifluoropropanamide 3H) 83 3-[4-(2-oxopyrrolidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.26(s, 1H), 7.79(s, 1H), propylpyrimidin-2- 7.60(d, 1H), 7.38(t, 1H), 7.27(d, 1H), 7.13(s, 1H), 4.11(t, ylamino]benzonitrile 2H), 2.75-2.55(m, 4H), 2.18(t, 2H), 1.77(q, 2H), 0.99(t, 3H) 84 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.57(d, 1H), (hexylamino)pyrrolidin-1-yl]- 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H), 3.90-3.20(m, 5H), 6-propylpyrimidin-2- 2.67(t, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), 1.90-1.85(m, ylamino}benzonitrile 1H), 1.72(q, 2H), 1.55-1.45(m, 2H), 1.40-1.20(m, 6H), 0.98(t, 3H), 0.95-0.85(m, 3H) 85 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.57(d, 1H), (propylamino)pyrrolidin-1- 7.34(t, 1H), 7.22(d, 1H), 5.75(s, 1H), 4.00-3.20(m, 5H), yl]pyrimidin-2- 2.65(t, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), 1.90-1.80(m, ylamino}benzonitrile 1H), 1.80-1.50(m, 6H), 1.00-0.90(m, 6H) 86 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.60(d, 1H), (cyclohexylmethylami- 7.50(brs, 1H), 7.33(t, 1H), 7.21(d, 1H), 5.73(s, 1H), 4.00- no)pyrrolidin-1-yl]-6- 3.10(m, 5H), 2.50-2.40(m, 4H), 2.25-2.15(m, 1H), 2.00- propylpyrimidin-2- 1.60(m, 9H), 1.50-1.40(m, 1H), 1.30-1.10(m, 4H), 0.98(t, ylamino}benzonitrile 3H) 87 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.59(d, 1H), (benzylamino)pyrrolidin-1- 7.52(brs, 1H), 7.40-7.15(m, 7H), 5.72(s, 1H), 3.87(s, yl]-6-propylpyrimidin-2- 2H), 3.80-3.10(m, 5H), 2.49(t, 2H), 2.25-2.15(m, 1H), ylamino}benzonitrile 2.00-1.90(m, 1H), 1.80-1.60(m, 2H), 0.98(t, 3H) 88 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.56(d, 1H), (phenethylamino)pyrrolidin- 7.50-7.00(m, 7H), 5.73(s, 1H), 3.95-3.75(m, 1H), 3.70- 1-yl]-6-propylpyrimidin-2- 3.30(m, 3H), 3.25-3.10(m, 1H), 3.00-2.90(m, 2H), 2.84(t, ylamino}benzonitrile 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), 1.90-1.85(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 89 (S)-3-{4-[3-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.63(d, 1H), phenylpropylamino)pyrrolidin- 7.39(t, 1H), 7.35-7.10(m, 6H), 5.75(s, 1H), 4.00-3.20(m, 1-yl]-6-propylpyrimidin-2- 5H), 2.80-2.60(m, 4H), 2.55(t, 2H), 2.30-2.00(m, 2H), ylamino}benzonitrile 2.00-1.90(m, 2H), 1.80-1.70(m, 2H), 1.01(t, 3H) 90 (S)-3-{4-[3-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.43(s, 1H), 7.53(d, 1H), fluorobenzylamino)pyrrolidin- 7.40-7.05(m, 6H), 6.95(t, 1H), 5.74(s, 1H), 3.87(s, 2H), 1-yl]-6-propylpyrimidin-2- 3.80-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m, 1H), 2.00- ylamino}benzonitrile 1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-10 Example Compound NMR Spectrum 91 (S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(s, 1H), 7.52(d, 1H), hydroxybenzylamino)pyrrolidin- 7.32(t, 1H), 7.25-7.15(m, 3H), 6.77(d, 2H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin- 3.78(s, 2H), 3.80-3.10(m, 5H), 2.48(t, 2H), 1.25-1.15(m, 2-ylamino}benzonitrile 1H), 2.00-1.90(m, 1H), 1.71(q, 2H), 0.97(t, 3H) 92 (S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.59(d, 1H), ethylbenzylamino)pyrrolidin- 7.40-7.10(m, 6H), 5.72(s, 1H), 3.84(s, 2H), 3.80-3.10(m, 1-yl]-6-propylpyrimidin-2- 5H), 2.63(q, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), 2.00- ylamino}benzonitrile 1.90(m, 1H), 1.72(q, 2H), 1.23(t, 3H), 0.98(t, 3H) 93 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.58(d, 1H), (isopentylamino)pyrrolidin- 7.33(t, 1H), 7.20(d, 1H), 7.00(brs, 1H), 5.74(s, 1H), 3.90- 1-yl]-6-propylpyrimidin-2- 3.00(m, 5H), 2.68(t, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), ylamino}benzonitrile 1.90-1.80(m, 1H), 1.80-1.50(m, 3H), 1.40(q, 2H), 0.98(t, 3H), 0.92(d, 6H) 94 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.56(d, 1H), (pentylamino)pyrrolidin-1- 7.34(t, 1H), 7.22(d, 1H), 7.00(brs, 1H), 5.75(s, 1H), 3.90- yl]-6-propylpyrimidin-2- 3.30(m, 5H), 2.67(t, 2H), 2.48(t, 2H), 2.25-2.15(m, 1H), ylamino}benzonitrile 2.00-1.60(m, 3H), 1.52(t, 2H), 1.40-1.20(m, 4H), 0.99(t, 3H), 0.92(t, 3H) 95 3-{4-[(3S)-3-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H), methylbutylamino)pyrrolidin- 7.33(t, 1H), 7.20(d, 1H), 7.03(brs, 1H), 5.74(s, 1H), 3.90- 1-yl]-6-propylpyrimidin-2- 3.10(m, 5H), 2.65-2.55(m, 1H), 2.50-2.40(m, 3H), 2.25- ylamino}benzonitrile 2.15(m, 1H), 1.90-1.80(m, 1H), 1.72(q, 2H), 1.50-1.35(m, 2H), 1.20-1.10(m, 1H), 0.98(t, 3H), 0.95-0.85(m, 6H) 96 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.55(d, 1H), (isobutylamino)pyrrolidin-1- 7.35(t, 1H), 7.23(d, 1H), 5.75(s, 1H), 3.90-3.10(m, 5H), yl]-6-propylpyrimidin-2- 2.55-2.45(m, 3H), 2.25-2.15(m, 1H), 1.90-1.85(m, 1H), ylamino}benzonitrile 1.80-1.60(m, 4H), 0.99(t, 3H), 0.94(d, 6H) 97 (S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.56(d, 1H), methoxybenzylamino)pyrrolidin- 7.33(t, 1H), 7.26(t, 2H), 7.21(d, 1H), 6.87(d, 2H), 5.73(s, 1-yl]-6-propylpyrimidin- 1H), 3.81(s, 2H), 3.80(s, 3H), 3.80-3.10(m, 5H), 2.48(t, 2-ylamino}benzonitrile 2H), 2.25-2.15(m, 1H), 2.00-1.90(m, 1H), 1.80-1.60(m, 2H), 0.98(t, 3H) 98 (S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.54(d, 1H), fluorobenzylamino)pyrrolidin- 7.40-7.30(m, 3H), 7.21(d, 1H), 7.01(d, 2H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.84(s, 2H), 3.80-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m, ylamino}benzonitrile 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 99 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.56(d, 1H), (cyclopropylmethylamino)pyrrol- 7.35(t, 1H), 7.24(d, 1H), 5.75(s, 1H), 3.90-3.20(m, 5H), idin-1-yl]-6-propylpyrimidin- 2.56(d, 2H), 2.49(t, 2H), 2.25-2.15(m, 1H), 2.00-1.90(m, 2-ylamino}benzonitrile 1H), 1.80-1.65(m, 2H), 1.00-0.90(m, 4H), 0.53(d, 2H), 0.17(d, 2H) 100 (S)-3-(4-{3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H), [bis(cyclopropylmethyl)ami- 7.32(t, 1H), 7.20(d, 1H), 7.08(brs, 1H), 5.73(s, 1H), 4.00- no]pyrrolidin-1-yl}-6- 3.10(m, 5H), 2.70-2.55(m, 4H), 2.48(t, 2H), 2.25-2.15(m, propylpyrimidin-2- 1H), 2.00-1.90(m, 1H), 1.80-1.65(m, 2H), 1.00-0.90(m, ylamino)benzonitrile 5H), 0.55(d, 4H), 0.18(d, 4H)

TABLE 1-11 Example Compound NMR Spectrum 101 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.52(s, 1H), 7.70-7.60(m, (pyridin-2- 2H), 7.51(brs, 1H), 7.33(t, 1H), 7.21(d, 1H), 7.15(t, 2H), ylmethylamino)pyrrolidin-1- 5.68(s, 1H), 3.95(s, 2H), 4.00-3.20(m, 5H), 2.48(t, 2H), yl]pyrimidin-2- 2.50-2.20(m, 2H), 1.71(q, 2H), 0.98(t, 3H) ylamino}benzonitrile 102 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.65-8.45(m, 3H), 7.70(t, (pyridin-3- 1H), 7.55(d, 1H), 7.40-7.15(m, 3H), 5.73(s, 1H), 3.89(s, ylmethylamino)pyrrolidin-1- 2H), 3.90-3.20(m, 5H), 2.48(t, 2H), 2.25-2.15(m, 1H), yl]pyrimidin-2- 2.00-1.90(m, 1H), 1.80-1.60(m, 2H), 0.98(t, 3H) ylamino}benzonitrile 103 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.60-8.40(m, 3H), 8.10(brs, (pyridin-4- 1H), 7.60-7.50(m, 1H), 7.40-7.15(m, 4H), 5.73(s, 1H), ylmethylamino)pyrrolidin-1- 3.90(s, 2H), 3.90-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m, yl]pyrimidin-2- 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.99(t, 3H) ylamino}benzonitrile 104 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.58(d, 1H), ethylbutylamino)pyrrolidin- 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H), 3.90-3.00(m, 5H), 1-yl]-6-propylpyrimidin-2- 2.48(t, 2H), 2.40(brs, 2H), 2.25-2.15(m, 1H), 1.88(brs, ylamino}benzonitrile 1H), 1.72(q, 2H), 0.98(t, 3H), 0.92(s, 9H) 105 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.58(d, 1H), (neopentylamino)pyrrolidin- 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H), 3.90-3.00(m, 5H), 1-yl]-6-propylpyrimidin-2- 2.48(t, 2H), 2.40(brs, 2H), 2.25-2.15(m, 1H), 1.88(brs, ylamino}benzonitrile 1H), 1.72(q, 2H), 0.98(t, 3H), 0.92(s, 9H) 106 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.60(d, 1H), fluorobenzylamino)pyrrolidin- 7.50-7.20(m, 4H), 7.12(t, 1H), 7.05(t, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.92(s, 2H), 3.90-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m, ylamino}benzonitrile 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 107 (S)-3-(4-propyl-6-{3-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.64(s, 1H), (trifluoromethyl)benzyl- 7.60-7.40(m, 4H), 7.33(t, 1H), 7.21(d, 1H), 5.73(s, 1H), amino]pyrrolidin-1-yl}pyrimidin- 3.94(s, 2H), 3.90-3.10(m, 5H), 2.49(t, 2H), 2.25-2.15(m, 2-ylamino)benzonitrile 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 108 (S)-3-(4-propyl-6-{3-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.48(s, 1H), 7.70-7.40(m, (trifluoromethyl)benzyl- 5H), 7.33(t, 1H), 7.21(d, 1H), 5.72(s, 1H), 3.94(s, 2H), amino]pyrrolidin-1-yl}pyrimidin- 3.90-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m, 1H), 2.00- 2-ylamino)benzonitrile 1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 109 (S)-4-({1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.53(d, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.25-7.15(m, 3H), 6.78(d, 2H), 5.74(s, 1H), propylpyrimidin-4- 3.79(s, 2H), 3.70-3.10(m, 5H), 2.49(s, 2H), 2.25-2.15(m, yl]pyrrolidin-3- 2H), 1.92(brs, 3H), 1.72(q, 2H), 0.98(t, 3H) ylamino}methyl)phenylacetate 110 (S)-3-(4-{3-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(s, 1H), 7.57(dd, 1H), (dimethylamino)benzyl- 7.35(t, 1H), 7.30-7.15(m, 3H), 6.71(d, 2H), 5.74(s, 1H), amino]pyrrolidin-1-yl}-6- 3.78(s, 2H), 3.80-3.30(m, 5H), 2.93(s, 6H), 2.50(t, 2H), propylpyrimidin-2- 2.25-2.15(m, 1H), 2.00-1.90(m, 1H), 1.73(q, 2H), 0.99(t, ylamino)benzonitrile 3H)

TABLE 1-12 Example Compound NMR Spectrum 111 (S)-3-(4-{3-[(1H-pyrrol-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(brs, 1H), 7.52(brs, 1H), yl)methylamino]pyrrolidin-1- 7.34(t, 1H), 7.23(d, 1H), 6.74(s, 1H), 6.14(d, 1H), 6.08(s, yl}-6-propylpyrimidin-2- 1H), 5.71(s, 1H), 3.90(s, 2H), 3.80-3.10(m, 5H), 2.49(t, ylamino)benzonitrile 2H), 2.25-2.15(m, 1H), 1.90-1.85(m, 1H), 1.71(q, 2H), 0.99(t, 3H) 112 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.59(d, 1H), (thiophen-2- 7.55(brs, 1H), 7.33(t, 1H), 7.30-7.20(m, 2H), 7.00- ylmethylamino)pyrrolidin-1- 6.90(m, 2H), 5.73(s, 1H), 4.08(s, 2H), 3.90-3.10(m, 5H), yl]pyrimidin-2- 2.48(t, 2H), 2.25-2.15(m, 1H), 2.00-1.90(m, 1H), 1.72(q, ylamino}benzonitrile 2H), 0.98(t, 3H) 113 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.57(d, 1H), (thiophen-3- 7.50(brs, 1H), 7.40-7.25(m, 2H), 7.25-7.15(m, 2H), ylmethylamino)pyrrolidin-1- 7.07(d, 1H), 5.73(s, 1H), 3.90(s, 2H), 3.90-3.10(m, 5H), yl]pyrimidin-2- 2.48(t, 2H), 2.25-2.15(m, 1H), 2.00-1.90(m, 1H), 1.72(q, ylamino}benzonitrile 2H), 0.98(t, 3H) 114 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(brs, 1H), 7.60(brs, 1H), (dibutylamino)pyrrolidin-1- 7.32(t, 1H), 7.20(d, 1H), 7.13(brs, 1H), 5.74(s, 1H), yl]-6-propylpyrimidin-2- 3.90(brs, 1H), 3.60-3.10(m, 4H), 2.75-2.40(m, 6H), 2.20- ylamino}benzonitrile 2.10(m, 1H), 2.00-1.90(m, 1H), 1.73(q, 2H), 1.50-1.20(m, 8H), 1.00-0.90(m, 9H) 115 (S)-3-(4-{3-bis[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.42(brs, 1H), 7.57(d, 1H), (methylthio)propyl]amino- 7.33(t, 1H), 7.20(d, 1H), 5.74(s, 1H), 3.90(brs, 1H), 3.65- pyrrolidin-1-yl}-6- 3.10(m, 4H), 2.70-2.60(m, 4H), 2.54(t, 4H), 2.49(t, 2H), propylpyrimidin-2- 2.25-2.15(m, 1H), 2.11(s, 6H), 2.00-1.90(m, 1H), 1.80- ylamino)benzonitrile 1.65(m, 6H), 0.98(t, 3H) 116 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.33(s, 1H), 7.58(d, 1H), (butylamino)pyrrolidin-1-yl]- 7.34(t, 1H), 7.22(d, 1H), 5.75(s, 1H), 3.90-3.10(m, 5H), 6-propylpyrimidin-2- 2.73(t, 2H), 2.49(t, 2H), 2.30-2.20(m, 1H), 2.10-1.95(m, ylamino}benzonitrile 1H), 1.72(q, 2H), 1.55-1.45(m, 2H), 1.45-1.30(m, 2H), 1.00-0.85(m, 6H) 117 (S)-3-(4-{3-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.57(d, 1H), (methylthio)propyl- 7.37(t, 1H), 7.30-7.20(m, 1H), 5.77(s, 1H), 3.90-3.10(m, amino]pyrrolidin-1-yl}- 5H), 2.90-2.70(m, 2H), 2.58(t, 2H), 2.51(t, 2H), 2.30- 6-propylpyrimidin-2- 2.20(m, 1H), 2.11(s, 3H), 2.00-1.90(m, 1H), 1.90-1.70(m, ylamino)benzonitrile 4H), 1.00(t, 3H) 118 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.45(d, 1H), 7.77(t, 1H), (propylamino)pyrrolidin-1- 7.41(t, 1H), 7.25(d, 1H), 5.98(s, 1H), 4.10-3.90(m, 2H), yl]pyrimidin-2- 3.85-3.50(m, 3H), 3.10-3.00(m, 2H), 2.60-2.40(m, 3H), ylamino}benzonitrile 2.30-2.20(m, 1H), 1.80-1.65(m, 3H), 1.50-1.40(m, 1H), dihydrochloride 1.10-0.90(m, 6H) 119 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H), 7.90-7.80(m, (cyclopropylmethyl- 1H), 7.60-7.45(m, 2H), 6.35(d, 1H), 4.25-3.65(m, 5H), amino)pyrrolidin-1-yl]- 3.15-2.90(m, 2H), 2.70-2.50(m, 3H), 2.50-2.25(m, 1H), 6-propylpyrimidin-2- 1.90-1.70(m, 2H), 1.20-1.10(m, 1H), 1.10-0.95(m, 3H), ylamino}benzonitrile 0.80-0.65(m, 2H), 0.50-0.40(m, 2H) dihydrochloride 120 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(brs, 1H), 7.83(d, 1H), (methylamino)pyrrolidin-1- 7.61-7.53(m, 2H), 6.34(s, 1H), 4.12-3.79(m, 5H), 2.81(s, yl]-6-propylpyrimidin-2- 3H), 2.69(dd, 2H), 2.58(brs, 1H), 2.38(brs, 1H), 1.85- ylamino}benzonitrile 1.76(m, 2H), 1.06(dd, 3H) dihydrochloride

TABLE 1-13 Example Compound NMR Spectrum 121 (S)-N-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.03(s, 1H), 7.41(d, 1H), (methylamino)pyrrolidin-1- 7.12(d, 1H), 7.04(d, 1H), 6.35(d, 1H), 5.82(s, 1H), 3.90- yl]-6-propylpyrimidin-2-yl}- 3.30(m, 5H), 2.50-2.40(m, 5H), 2.30-2.20(m, 1H), 2.00- 1H-indol-6-amine 1.90(m, 1H), 1.73(q, 2H), 0.99(t, 3H) 122 (S)-N-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.66(s, 1H), 7.57(d, 1H), (methylamino)pyrrolidin-1- 7.27(d, 1H), 7.04(d, 1H), 6.46(d, 1H), 6.19(s, 1H), 4.10- yl]-6-propylpyrimidin-2-yl}- 3.60(m, 5H), 2.78(s, 3H), 2.62(t, 2H), 2.55(brs, 1H), 1H-indol-6-amine 2.31(brs, 1H), 1.75(q, 2H), 1.04(t, 3H) hydrochloride 123 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.97(d, 1H), 7.65-7.55(m, (methylamino)pyrrolidin-1- 1H), 7.21(t, 1H), 6.30(d, 1H), 4.15-3.75(m, 5H), 2.79(d, yl]-6-propylpyrimidin-2-yl}-3- 3H), 2.69(t, 2H), 2.65-2.50(m, 1H), 2.50-2.25(m, 1H), (trifluoromethyl)benzene- 1.90-1.70(m, 2H), 1.07(t, 3H) 1,4-diamine dihydrochloride 124 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.98(brs, 1H), cyanophenylamino)-6- 7.60-7.50(m, 1H), 7.34(t, 1H), 7.22(d, 1H), 6.27(brs, 1H), propylpyrimidin-4- 5.53(s, 1H), 4.24(brs, 1H), 3.80-3.20(m, 5H), 2.50- yl]pyrrolidin-3- 2.35(m, 2H), 2.30-2.00(m, 2H), 1.70-1.50(m, 2H), 1.46(d, yl}isopropane-2- 6H), 0.95(t, 3H) sulfonamide 125 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.43(s, 1H), 7.61(d, 1H), cyanophenylamino)-6- 7.35(t, 1H), 7.24(d, 1H), 5.66(s, 1H), 4.24(brs, 1H), 3.90- propylpyrimidin-4- 3.30(m, 5H), 3.08(s, 3H), 2.50-2.20(m, 4H), 1.67(q, 2H), yl]pyrrolidin-3- 0.98(t, 3H) yl}methanesulfonamide 126 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 8.00-7.90(m, cyanophenylamino)-6- 2H), 7.54(d, 1H), 7.33(t, 1H), 7.30-7.15(m, 3H), 5.54(s, propylpyrimidin-4- 1H), 4.10(brs, 1H), 3.70-3.30(m, 4H), 2.50-2.25(m, 2H), yl]pyrrolidin-3-yl}-4- 2.20-2.00(m, 2H), 1.58(q, 2H), 0.91(t, 3H) fluorobenzenesulfonamide 127 3-{4-[(3S)-3-(sec- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.58(d, 1H), butylamino)pyrrolidin-1-yl]- 7.33(dd, 1H), 7.20(d, 1H), 7.10(s, 1H), 5.74(s, 1H), 4.10- 6-propylpyrimidin-2- 3.10(m, 5H), 2.71-2.67(m, 1H), 2.48(dd, 2H), 2.26- ylamino}benzonitrile 2.21(m, 1H), 1.77-1.67(m, 3H), 1.52-1.46(m, 1H), 1.39- 1.34(m, 1H), 1.10-1.07(m, 3H), 0.98(t, 3H), 0.94-0.90(m, 3H) 128 (S)-3-{4-[3-(pentan-3- ¹H-NMR(400 MHz, CDCl₃) δ 10.02(brs, 1H), 8.42(s, 1H), ylamino)pyrrolidin-1-yl]-6- 7.70(d, 1H), 7.35(dd, 1H), 7.24(d, 1H), 5.71(s, 1H), 3.88- propylpyrimidin-2- 3.12(m, 5H), 2.53-2.45(m, 3H), 2.26-2.18(m, 1H), 2.10(s, ylamino}benzonitrile 3H), 1.94-1.88(m, 1H), 1.76-1.67(m, 2H), 1.52-1.44(m, 4H), 0.98(t, 3H), 0.95-0.90(m, 6H) 129 (S)-3-{4-[3-(2,6- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(brs, 1H), 7.65(brs, 1H), dimethylheptan-4- 7.33(dd, 1H), 7.22-7.20(m, 2H), 5.74(s, 1H), 3.88- ylamino)pyrrolidin-1-yl]-6- 3.12(m, 5H), 2.83-2.82(m, 1H), 2.48(dd, 2H), 2.24- propylpyrimidin-2- 2.21(m, 1H), 1.84-1.62(m, 7H), 1.39-1.36(m, 1H), 1.26- ylamino}benzonitrile 1.22(m, 1H), 1.14-1.02(m, 3H), 0.98(t, 3H), 0.88-0.81(m, 9H)

TABLE 1-14 Example Compound NMR Spectrum 130 (S)-3-{4-[3-(4,4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.62(brs, 2H), dimethylpentan-2- 7.33(dd, 1H), 7.21(d, 1H), 5.73(s, 1H), 3.84-3.07(m, 5H), ylamino)pyrrolidin-1-yl]-6- 2.85-2.81(m, 1H), 2.49(dd, 2H), 2.27-2.20(m, 1H), 1.77- propylpyrimidin-2- 1.70(m, 3H), 1.37-1.30(m, 2H), 1.12(d, 3H), 1.04-0.81(m, ylamino}benzonitrile 12H) 131 (S)-3-{4-[3-(3-hydroxy-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.49-8.35(m, 1H), 7.68(brs, methylbutan-2- 1H), 7.37-7.33(m, 1H), 7.25-7.23(m, 1H), 5.71(s, 1H), ylamino)pyrrolidin-1-yl]-6- 3.92-3.22(m, 5H), 2.54-2.49(m, 3H), 2.29-2.25(m, 1H), propylpyrimidin-2- 2.12-2.06(m, 1H), 1.75-1.66(m, 2H), 1.21(d, 3H), 1.16- ylamino}benzonitrile 1.13(m, 3H), 1.05(s, 3H), 1.00(t, 3H) 132 (S)-3-{4-[3-(heptan-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.62(brs, 1H), ylamino)pyrrolidin-1-yl]-6- 7.47(brs, 1H), 7.33(m, 1H), 7.20(d, 1H), 5.71(s, 1H), propylpyrimidin-2- 3.82-3.06(m, 5H), 2.58-2.56(m, 1H), 2.49(dd, 2H), 2.24- ylamino}benzonitrile 2.16(m, 1H), 1.94-1.90(m, 1H), 1.77-1.68(m, 2H), 1.43- 1.36(m, 8H), 1.00(t, 3H), 0.95-0.85(m, 6H) 133 (S)-3-{4-[3-(n-hexan-2- ¹H-NMR(400 MHz, CDCl₃) δ 9.35(brs, 1H), 8.42(brs, 1H), ylamino)pyrrolidin-1-yl]-6- 7.34(dd, 1H), 7.23(d, 1H), 5.71(s, 1H), 3.85-3.10(m, 5H), propylpyrimidin-2- 2.75-2.71(m, 1H), 2.50(dd, 2H), 2.26-2.22(m, 1H), 1.94- ylamino}benzonitrile 1.87(m, 1H), 1.74-1.69(m, 2H), 1.45-1.31(m, 6H), 1.11- 0.88(m, 9H) 134 (S)-3-{4-[3-(5-methylhexan- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(brs, 2H), 7.63(d, 1H), 2-ylamino)pyrrolidin-1-yl]-6- 7.33(dd, 1H), 7.21(d, 1H), 5.72(s, 1H), 3.85-3.10(m, 5H), propylpyrimidin-2- 2.74-2.70(m, 1H), 2.49(dd, 2H), 2.26-2.21(m, 1H), 1.94- ylamino}benzonitrile 1.87(m, 1H), 1.74-1.69(m, 2H), 1.54-1.17(m, 5H), 1.10- 1.08(m, 3H), 0.98(t, 3H), 0.90-0.86(m, 6H) 135 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.72(d, 1H), (cyclohexylamino)pyrrolidin- 7.35(dd, 1H), 7.25(d, 1H), 5.69(s, 1H), 3.95-3.15(m, 5H), 1-yl]-6-propylpyrimidin-2- 2.54-2.52(m, 3H), 2.27-2.23(m, 2H), 1.93(brs, 3H), 1.78- ylamino}benzonitrile 1.63(m, 5H), 1.32-1.15(m, 5H), 0.98(t, 3H) 136 (S)-tert-butyl 2-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.42(s, 1H), 7.58(d, 1H), cyanophenylamino)-6- 7.33(dd, 1H), 7.20(d, 1H), 5.73(s, 1H), 4.97(brs, 1H), propylpyrimidin-4- 3.72-3.25(m, 9H), 2.81(brs, 1H), 2.48(dd, 2H), 2.23- yl]pyrrolidin-3- 2.18(m, 1H), 1.88(brs, 1H), 1.76-1.71(m, 2H), 1.44(s, ylamino}ethylcarbamate 9H), 0.98(t, 3H) 137 (S)-3-{4-[3-(1- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.57(d, 1H), benzylpiperidin-4- 7.35-7.19(m, 6H), 7.09(brs, 1H), 5.73(s, 1H), 3.76- ylamino)pyrrolidin-1-yl]-6- 3.58(m, 3H), 3.51(s, 2H), 3.51-3.05(m, 2H), 2.87(d, 2H), propylpyrimidin-2- 2.61-2.54(m, 1H), 2.47(dd, 2H), 2.23-2.19(m, 1H), ylamino}benzonitrile 2.05(dd, 2H), 1.89-1.85(m, 3H), 1.76-1.67(m, 2H), 1.46- 1.37(m, 2H), 0.97(t, 3H) 138 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.59(d, 1H), (isopropylamino)pyrrolidin- 7.32(dd, 1H), 7.20(d, 1H), 7.11(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 4.10-2.99(m, 5H), 2.99-2.93(m, 1H), 2.48(dd, 2H), 2.28- ylamino}benzonitrile 2.21(m, 1H), 1.84(brs, 1H), 1.77-1.67(m, 2H), 1.11(dd, 6H), 0.97(t, 3H) 139 (S)-3-{4-[3-(1- ¹H-NMR(400 MHz, CDCl₃) δ 8.54(brs, 1H), 7.47-7.40(m, benzoylpiperidin-4- 6H), 7.33(dd, 1H), 7.21(d, 1H), 5.73(s, 1H), 4.63(brs, ylamino)pyrrolidin-1-yl]-6- 1H), 4.23-2.90(m, 9H), 2.48(dd, 2H), 2.27-2.23(m, 1H), propylpyrimidin-2- 2.11-1.69(m, 7H), 0.98(t, 3H) ylamino}benzonitrile

TABLE 1-15 Example Compound NMR Spectrum 140 (S)-3-{4-[3-(1- ¹H-NMR(400 MHz, CDCl₃) δ 8.50-8.37(m, 1H), 7.60- acetylpiperidin-4- 7.49(m, 1H), 7.32(dd, 1H), 7.20(d, 1H), 7.14(brs, 1H), ylamino)pyrrolidin-1-yl]-6- 5.74(s, 1H), 4.51(d, 1H), 3.89-3.38(m, 6H), 3.15(dd, 1H), propylpyrimidin-2- 2.84(brs, 1H), 2.76(dd, 1H), 2.48(dd, 2H), 2.26-2.20(m, ylamino}benzonitrile 1H), 2.10(s, 3H), 1.97-1.89(m, 3H), 1.76-1.67(m, 2H), 1.30-1.25(m, 2H), 0.98(t, 3H) 141 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(brs, 1H), 7.56(brs, 1H), (cyclooctylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d, 1H), 7.16(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.89-3.38(m, 5H), 2.79(brs, 1H), 2.53-2.45(m, 4H), 2.23- ylamino}benzonitrile 2.09(m, 3H), 2.01-1.50(m, 14H), 0.98(t, 3H) 142 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(brs, 1H), 7.59(d, 1H), (cyclobutylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d, 1H), 7.00(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.83-3.32(m, 6H), 2.47(dd, 2H), 2.29-2.15(m, 3H), ylamino}benzonitrile 1.85(brs, 1H), 1.79-1.64(m, 6H), 0.98(t, 3H) 143 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(brs, 1H), 7.58(d, 1H), (cyclopentylamino)pyrrolidin- 7.32(dd, 1H), 7.19(d, 1H), 7.18(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.99-3.14(m, 6H), 2.47(dd, 2H), 2.28-2.20(m, 1H), 1.93- ylamino}benzonitrile 1.88(m, 3H), 1.76-1.67(m, 4H), 1.64-1.51(m, 2H), 1.38- 1.24(dd, 2H), 0.97(t, 3H) 144 (S)-tert-butyl 3-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.59(d, 1H), cyanophenylamino)-6- 7.32(dd, 1H), 7.21(brs, 1H), 7.20(d, 1H), 5.76(brs, 1H), propylpyrimidin-4- 4.65(d, 4H), 3.97-3.40(m, 6H), 2.48(dd, 2H), 2.26- yl]pyrrolidin-3- 2.05(m, 2H), 1.74-1.69(m, 2H), 1.49(s, 9H), 0.97(t, 3H) ylamino}azetidine-1- carboxylate 145 (S)-3-(4-{3-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.70(d, 1H), (benzyloxy)ethylamino]pyrrolidin- 7.37-7.23(m, 7H), 5.69(s, 1H), 4.53(s, 2H), 3.85-3.19(m, 1-yl}-6-propylpyrimidin-2- 7H), 2.89(brs, 2H), 2.52(dd, 2H), 2.25-2.17(m, 1H), ylamino)benzonitrile 2.10(s, 3H), 1.94(brs, 1H), 1.76-1.67(m, 2H), 0.99(t, 3H) 146 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.61(s, 1H), cyanophenylamino)-6- 7.54(s, 1H), 7.33(t, 1H), 7.19(d, 1H), 5.81(m, 1H), propylpyrimidin-4- 5.80(s, 1H), 4.62(m, 1H), 3.78-3.01(m, 4H), 2.48(t, 2H), yl]pyrrolidin-3- 2.32(m, 1H), 2.23(m, 2H), 2.01(m, 1H), 1.72(m, 2H), yl}propionamide 1.17(t, 3H), 0.98(t, 3H) 147 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.71(s, 1H), cyanophenylamino)-6- 7.35(t, 1H), 7.23(d, 1H), 5.77(s, 1H), 5.71(s, 1H), propylpyrimidin-4- 4.59(m, 1H), 3.81-3.22(m, 4H), 2.47(t, 2H), 2.34(m, 1H), yl]pyrrolidin-3-yl}pivalamide 2.01(m, 1H), 1.67(q, 2H), 1.21(s, 9H), 0.98(t, 3H) 148 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.25(s, 1H), 7.53(s, 1H), cyanophenylamino)-6- 7.26(t, 1H), 7.13(d, 1H), 7.09(brs, 1H), 5.69(s, 1H), propylpyrimidin-4- 4.53(m, 1H), 3.75-3.21(m, 4H), 2.43(t, 2H), 2.25(m, 1H), yl]pyrrolidin-3-yl}-2,2- 1.86(m, 1H), 1.66(m, 2H), 1.47(m, 2H), 1.09(s, 6H), dimethylbutanamide 0.91(t, 3H), 0.75(t, 3H)

TABLE 1-16 Example Compound NMR Spectrum 149 (S,E)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(s, 1H), 7.61(s, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.22(d, 1H), 7.06(s, 1H), 6.45(m, 1H), propylpyrimidin-4- 5.86(m, 1H), 5.76(s, 1H), 4.66(m, 1H), 3.81-3.37(m, 4H), yl]pyrrolidin-3-yl}-2- 2.48(t, 2H), 2.34(m, 1H), 2.05(m, 1H), 1.85(s, 3H), methylbut-2-enamide 1.71(m, 5H), 0.98(t, 3H) 150 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.60(s, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.20(d, 1H), 7.06(s, 1H), 5.75(s, 1H), propylpyrimidin-4- 5.67(m, 1H), 4.60(m, 1H), 3.77-3.34(m, 4H), 2.50(t, 2H), yl]pyrrolidin-3- 2.31(m, 1H), 2.17(t, 2H), 2.02(m, 1H), 1.76-1.62(m, 4H), yl}hexanamide 1.31(m, 6H), 0.98(t, 3H), 0.89(t, 3H) 151 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.59(s, 1H), cyanophenylamino)-6- 7.35(t, 1H), 7.27-7.12(m, 7H), 5.70(s, 1H), 5.57(m, 1H), propylpyrimidin-4- 4.55(m, 1H), 3.69(m, 4H), 2.97(t, 2H), 2.49(m, 4H), yl]pyrrolidin-3-yl}-3- 2.22(m, 1H), 1.73(m, 1H), 1.69(m, 2H), 0.98(t, 3H) phenylpropanamide 152 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 8.26(s, 1H), cyanophenylamino)-6- 7.52(m, 2H), 7.39-7.31(m, 2H), 7.22-7.16(m, 2H), propylpyrimidin-4- 7.09(m, 1H), 5.80(m, 1H), 5.65(s, 1H), 4.58(m, 1H), yl]pyrrolidin-3-yl}-2-(1H- 3.76(s, 2H), 3.34-3.20(m, 4H), 2.46(t, 2H), 2.25(m, 1H), indol-3-yl)acetamide 1.71(m, 3H), 0.97(t, 3H) 153 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(s, 1H), 7.58(d, 1H), cyanophenylamino)-6- 7.32(t, 1H), 7.20(d, 2H), 6.97(m, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.59(m, 1H), 3.83-3.34(m, 4H), 2.51(t, 2H), 2.31(m, 1H), yl]pyrrolidin-3-yl}-2-hydroxy- 2.03(m, 1H), 1.71(m, 2H), 1.47(s, 6H), 0.98(t, 3H) 2-methylpropanamide 154 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.28(s, 1H), 7.62(s, 1H), cyanophenylamino)-6- 7.48(s, 1H), 7.32(t, 1H), 7.18(d, 1H), 7.08(d, 1H), 6.80(d, propylpyrimidin-4- 1H), 5.70(s, 1H), 5.65(m, 1H), 4.56(m, 1H), 3.73(s, 3H), yl]pyrrolidin-3-yl}-3-(4- 3.69-3.00(m, 4H), 2.90(t, 2H), 2.46(m, 4H), 2.21(m, 1H), methoxyphenyl)propanamide 1.90(m, 1H), 1.69(m, 2H), 0.98(t, 3H) 155 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.01(s, 1H), 7.50(s, 1H), cyanophenylamino)-6- 7.37(t, 1H), 7.20(d, 1H), 7.04(d, 2H), 6.78(d, 2H), 5.69(s, propylpyrimidin-4- 1H), 5.47(m, 1H), 4.55(m, 1H), 3.75-3.24(m, 4H), yl]pyrrolidin-3-yl}-3-(4- 2.89(m, 2H), 2.49(m, 4H), 1.68(m, 2H), 0.96(t, 3H) hydroxyphenyl)propanamide 156 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.78(s, 1H), cyanophenylamino)-6- 7.65(s, 1H), 7.33(t, 1H), 7.19(d, 1H), 5.59(s, 1H), propylpyrimidin-4- 4.61(m, 1H), 3.65-3.00(m, 4H), 2.89(m, 2H), 2.48(m, yl]pyrrolidin-3-yl}-4- 4H), 2.22(s, 3H + 1H), 2.06(m, 1H), 1.64(m, 2H), 0.95(t, oxopentanamide 3H) 157 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(s, 1H), 7.59(d, 1H), cyanophenylamino)-6- 7.47(s, 1H), 7.33(t, 1H), 7.19(d, 1H), 6.83(d, 1H), 5.73(s, propylpyrimidin-4- 1H), 4.65(m, 1H), 4.14(s, 2H), 3.81-3.43(m, 4H), 2.48(t, yl]pyrrolidin-3-yl}-2- 2H), 2.33(m, 1H), 2.05(m, 1H), 1.70(m, 2H), 0.98(t, 3H) hydroxyacetamide

TABLE 1-17 Example Compound NMR Spectrum 158 (S)-2-benzyloxy-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.64(s, 1H), cyanophenylamino)-6- 7.31(m, 5H), 7.20(m, 1H), 6.74(d, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.65(m, 1H), 4.57(s, 2H), 3.99(s, 2H), 3.79-3.37(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.51(t, 2H), 2.32(m, 1H), 2.02(m, 1H), 1.70(m, 2H), 0.98(t, 3H) 159 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.63(s, 1H), cyanophenylamino)-6- 7.36-7.20(m, 4H), 7.02(t, 1H), 6.90(d, 2H), 6.71(m, 1H), propylpyrimidin-4- 5.75(s, 1H), 4.69(m, 1H), 4.51(s, 2H), 3.83-3.42(m, 4H), yl]pyrrolidin-3-yl}-2- 2.51(t, 2H), 2.34(m, 1H), 2.04(m, 1H), 1.70(m, 2H), phenoxyacetamide 0.98(t, 3H) 160 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 7.60(s, 1H), cyanophenylamino)-6- 7.33(m, 2H), 7.21(d, 1H), 5.76(s, 1H), 4.65(m, 1H), 3.93- propylpyrimidin-4- 3.31(m, 4H), 2.96(s, 2H), 2.49(t, 2H), 2.34(m, 1H), yl]pyrrolidin-3-yl}-2- 2.28(s, 6H), 2.03(m, 1H), 1.71(m, 2H), 0.97(t, 3H) (dimethylamino)acetamide 161 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.91(s, 1H), 8.37(s, 1H), cyanophenylamino)-6- 7.62(s, 1H), 7.35(t, 1H), 7.23(d, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.57(m, 1H), 3.74(m, 2H), 2.96(m, 2H), 2.60(m, 2H), yl]pyrrolidin-3-yl}-3- 2.50(m, 2H), 2.41(m, 2H), 2.28(m, 7H), 2.00(m, 1H), (dimethylamino)propanamide 1.71(q, 2H), 0.98(t, 3H) 162 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(s, 1H), 8.02(s, 1H), cyanophenylamino)-6- 7.60(d, 1H), 7.34(t, 2H), 7.20(d, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.56(m, 1H), 3.74-3.49(m, 4H), 2.55-2.41(m, 8H), 2.35(s, yl]pyrrolidin-3-yl}-4- 6H), 2.00(m, 1H), 1.86(m, 1H), 1.69(m, 2H), 0.96(t, 3H) dimethylaminobutanamide 163 N-(S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s, 1H), 7.63(s, 1H), cyanophenylamino)-6- 7.32(t, 1H), 7.22(m, 1H), 7.18(s, 1H), 6.72(m, 1H), propylpyrimidin-4- 5.76(s, 1H), 4.68(m, 1H), 3.95(s, 2H), 3.81(m, 2H), yl]pyrrolidin-3-yl}-2- 3.55(m, 2H), 3.41(m, 2H), 2.51(t, 2H), 2.34(m, 1H), ethoxyacetamide 2.06(m, 1H), 1.71(m, 2H), 1.23(t, 3H), 0.96(t, 3H) 164 N-(S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 7.61(s, 1H), cyanophenylamino)-6- 7.40(s, 1H), 7.36(t, 1H), 7.20(d, 1H), 7.13(s, 1H), 5.76(s, propylpyrimidin-4- 1H), 4.67(m, 1H), 4.01(s, 2H), 3.80(m, 2H), 3.76(d, 2H), yl]pyrrolidin-3-yl}-2-(2- 3.66(d, 2H), 3.50(m, 2H), 3.32(s, 3H), 2.49(t, 2H), methoxyethoxy)acetamide 2.33(m, 1H), 2.06(m, 1H), 1.71(m, 2H), 0.98(t, 3H) 165 (S)-benzyl 2-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 7.64(d, 1H), cyanophenylamino)-6- 7.34(m, 5H), 7.20(d, 1H), 6.58(s, 1H), 5.70(s, 1H), propylpyrimidin-4- 5.46(m, 1H), 5.12(s, 2H), 4.61(m, 1H), 3.89(m, 2H), yl]pyrrolidin-3-ylamino}-2- 3.80-3.25(m, 4H), 2.48(t, 2H), 2.28(m, 1H), 2.01(m, 1H), oxoethylcarbamate 1.70(m, 2H), 0.98(t, 3H) 166 (S)-tert-butyl 3-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.64(s, 1H), cyanophenylamino)-6- 7.31(t, 1H), 7.20(d, 1H), 7.11(s, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.75(m, 1H), 4.61(m, 1H), 3.76-3.25(m, 4H), 3.18(m, yl]pyrrolidin-3-ylamino}-3- 2H), 2.50(m, 2H), 2.32(m, 1H), 2.27(m, 2H), 2.17(m, oxobutylcarbamate 1H), 1.81(m, 2H), 1.69(m, 2H), 1.37(s, 9H), 0.96(t, 3H)

TABLE 1-18 Example Compound NMR Spectrum 167 (S)-tert-butyl 4-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.60(s, 1H), cyanophenylamino)-6- 7.34-7.27(m, 1H), 7.18(d, 1H), 5.90(m, 1H), 5.74(s, 1H), propylpyrimidin-4- 4.61(m, 1H), 4.14(m, 2H), 3.78-3.34(m, 4H), 2.72(m, yl]pyrrolidin-3- 2H), 2.23(t, 2H), 2.11(m, 2H), 2.01(m, 1H), 1.81-1.71(m, ylcarbamoyl}piperidine-1- 6H), 1.45(s, 9H), 0.98(t, 3H) carboxylate 168 (R)-2-methyl-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.80(dd, 1H), 7.65(dd, 1H), methylpyrrolidin-1-yl)-6- 7.44(d, 1H), 6.24(d, 1H), 4.35(m, 1H), 3.90-3.45(m, 2H), propylpyrimidin-2- 2.70-2.60(m, 2H), 2.52(s, 3H), 2.30-2.00(m, 3H), 1.90- ylamino]benzonitrile 1.70(m, 3H), 1.40-1.20(m, 3H), 1.05(t, 3H) hydrochloride 169 (R)-2-amino-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 7.63(d, 1H), 7.35(dd, 1H), methylpyrrolidin-1-yl)-6- 6.85(d, 1H), 6.15(d, 1H), 4.30(m, 1H), 3.80-3.40(m, 2H), propylpyrimidin-2- 2.60(t, 2H), 2.30-2.00(m, 3H), 1.90-1.70(m, 3H), 1.30- ylamino]benzonitrile 1.20(m, 3H), 1.04(t, 3H) hydrochloride 170 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s, 1H), 7.45(dd, 1H), (methylamino)pyrrolidin-1- 7.20-7.10(m, 2H), 5.72(s, 1H), 3.90-3.10(m, 5H), 2.50- yl]-6-propylpyrimidin-2- 2.40(m, 8H), 2.25-2.10(m, 1H), 1.90(brs, 1H), 1.71(q, ylamino}benzonitrile 2H), 0.97(t, 3H) 171 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.63(brs, 1H), (ethylamino)pyrrolidin-1-yl]- 7.48(d, 1H), 7.17(d, 1H), 5.71(s, 1H), 3.90-3.10(m, 5H), 6-propylpyrimidin-2- 2.80-2.70(m, 2H), 2.60-2.40(m, 5H), 2.25-2.15(m, 1H), ylamino}-2- 2.00-1.80(m, 1H), 1.71(q, 2H), 1.15(t, 3H), 0.98(t, 3H) methylbenzonitrile 172 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.63(dd, 1H), (ethylamino)pyrrolidin-1-yl]- 7.27(d, 1H), 5.96(s, 1H), 4.10-3.90(m, 2H), 3.85-3.50(m, 6-propylpyrimidin-2- 3H), 3.17(q, 2H), 2.60-2.45(m, 3H), 2.45(s, 3H), 2.30- ylamino}-2- 2.20(m, 1H), 1.74(q, 2H), 1.36(t, 3H), 0.98(t, 3H) methylbenzonitrile hydrochloride 173 5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.63(dd, 1H), (ethylamino)pyrrolidin-1-yl]- 7.27(d, 1H), 5.96(s, 1H), 4.10-3.90(m, 2H), 3.85-3.50(m, 6-propylpyrimidin-2- 3H), 3.17(q, 2H), 2.60-2.45(m, 3H), 2.45(s, 3H), 2.30- ylamino}-2- 2.20(m, 1H), 1.74(q, 2H), 1.36(t, 3H), 0.98(t, 3H) methylbenzonitrile hydrochloride 174 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.32(s, 1H), 7.63(dd, 1H), (methylamino)pyrrolidin-1- 7.27(d, 2H), 5.97(s, 1H), 3.95-3.62(m, 5H), 2.78(s, 3H), yl]-6-propylpyrimidin-2- 2.54-2.49(m, 3H), 2.44(s, 3H), 2.28-2.23(m, 1H), 1.76- ylamino}benzonitrile 1.70(m, 2H), 0.97(t, 3H) hydrochloride 175 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.65(s, 1H), 7.70(d, 1H), (methylamino)pyrrolidin-1- 7.37(d, 1H), 5.77(s, 1H), 4.00-3.30(m, 5H), 2.60-2.40(m, yl]-6-propylpyrimidin-2-yl}-3- 5H), 2.25-2.15(m, 1H), 2.05-1.95(m, 1H), 1.70-1.60(m, nitrobenzene-1,4-diamine 2H), 0.99(t, 3H)

TABLE 1-19 Example Compound NMR Spectrum 176 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.64(s, 1H), 7.70(d, 1H), (ethylamino)pyrrolidin-l-yl]- 7.28(d, 1H), 5.77(s, 1H), 4.00-3.30(m, 5H), 2.80-2.70(m, 6-propylpyrimidin-2-yl}-3- 2H), 2.51(t, 2H), 2.30-2.20(m, 1H), 2.00-1.90(m, 1H), nitrobenzene-1,4-diamine 1.72(q, 2H), 1.17(t, 3H), 0.99(t, 3H) 177 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.66(s, 1H), 7.76(d, 1H), (ethylamino)pyrrolidin-l-yl]- 7.47(d, 1H), 6.05(s, 1H), 4.10-3.90(m, 2H), 3.80-3.50(m, 6-propylpyrimidin-2-yl}-3- 3H), 3.25-3.10(m, 2H), 2.60-2.45(m, 3H), 2.30-2.20(m, nitrobenzene-1,4-diamine 1H), 1.78(q, 2H), 1.37(t, 3H), 1.00(t, 3H) hydrochloride 178 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.44(s, 1H), 7.79(d, 1H), (methylamino)pyrrolidin-1- 7.39(t, 1H), 7.24(d, 1H), 5.99(s, 1H), 3.96(m, 2H), 3.75- yl]-6-propylpyrimidin-2- 3.65(m, 3H), 2.80(s, 3H), 2.53(m, 1H + 2H), 2.26(m, 1H), ylamino}benzonitrile 1.73(m, 2H), 0.99(s, 3H) hydrochloride 179 (R)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.13(d, 1H), 7.87(dd, 1H), (aminomethyl)pyrrolidin-1- 7.60-7.45(m, 2H), 6.27(d, 1H), 4.20-3.60(m, 3H), 3.50- yl]-6-propylpyrimidin-2- 3.35(m, 1H), 3.20-3.00(m, 2H), 2.80-2.60(m, 3H), 2.45- ylamino}benzonitrile 2.25(m, 1H), 2.00-1.90(m, 1H), 1.79(q, 2H), 1.05(t, 3H) dihydrochloride 180 (S)-2-fluoro-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.90-8.80(m, 1H), 8.45- (methylamino)pyrrolidin-1- 8.35(m, 1H), 7.24(t, 1H), 5.98(s, 1H), 4.00-3.80(m, 2H), yl]-6-propylpyrimidin-2- 3.80-3.55(m, 3H), 2.79(s, 3H), 2.55-2.45(m, 3H), 2.30- ylamino}benzonitrile 2.20(m, 1H), 1.74(q, 2H), 0.98(t, 3H) hydrochloride 181 (S)-2-fluoro-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.40(brs, 1H), 7.90-7.75(m, (ethylamino)pyrrolidin-1-yl]- 1H), 7.24(t, 1H), 5.98(s, 1H), 4.10-3.85(m, 2H), 3.85- 6-propylpyrimidin-2- 3.50(m, 3H), 3.18(q, 2H), 2.60-2.40(m, 3H), 2.30-2.20(m, ylamino}benzonitrile 1H), 1.74(q, 2H), 1.36(t, 3H), 0.98(t, 3H) hydrochloride 182 5-[4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.00(m, 1H), 7.95- yl)-6-propylpyrimidin-2- 7.85(m, 1H), 7.42(t, 1H), 6.32(s, 1H), 4.20-3.60(m, 5H), ylamino]-2- 2.68(t, 2H), 2.60-2.40(m, 1H), 2.30-2.15(m, 1H), 1.90- fluorobenzonitrile 1.70(m, 2H), 1.06(t, 3H) dihydrochloride 183 N-(4-fluorophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.63-7.58(m, 2H), 7.00- methyl-6-(pyrrolidin-1- 6.95(m, 3H), 5.59(s, 1H), 3.53-3.41(m, 4H), 2.25(s, 3H), yl)pyrimidin-2-amine 1.99(brs, 4H) 184 (3R,5S)-1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.48(dd, 2H), 6.97(dd, 2H), fluorophenyl)-6- 5.66(s, 1H), 4.56(s, 1H), 4.41(d, 1H), 3.78(d, 1H), 3.62- propylpyrimidin-4-yl]-5- 3.45(m, 4H), 2.43(dd, 2H), 2.13(brs, 1H), 1.97(brs, 1H), (hydroxymethyl)pyrrolidin-3- 1.71-1.65(m, 2H), 0.96(t, 3H) ol 185 (S)-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 8.05(s, 1H), ylamino)-6-propylpyrimidin- 7.49(d, 1H), 7.04(dd, 1H), 6.97(dd, 1H), 6.90(brs, 1H), 4-yl]pyrrolidin-2-yl}methanol 6.43(d, 1H), 5.70(s, 1H), 4.39(brs, 1H), 3.75(dd, 1H), 3.59(dd, 1H), 3.46(brs, 1H), 3.35-3.27(m, 1H), 2.48(dd, 2H), 2.04-1.96(m, 3H), 1.78-1.69(m, 3H), 0.97(t, 3H)

TABLE 1-20 Example Compound NMR Spectrum 186 (R)-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H), 8.03(s, 1H), ylamino)-6-propylpyrimidin- 7.48(d, 1H), 7.01-6.80(m, 3H), 6.42(s, 1H), 5.69(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 4.86(brs, 1H), 4.38(brs, 1H), 3.74(dd, 1H), 3.57(dd, 1H), 3.44(brs, 1H), 3.29(brs, 1H), 2.48(dd, 2H), 2.04-1.96(m, 3H), 1.77-1.68(m, 3H), 0.96(t, 3H) 187 {1-[2-(1H-indol-6-ylamino)- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H), 8.02(s, 1H), 6-propylpyrimidin-4- 7.47(dd, 1H), 7.02-6.89(m, 3H), 6.42(d, 1H), 5.69(s, 1H), yl]pyrrolidin-2-yl}methanol 4.86(brs, 1H), 4.38(brs, 1H), 3.75(dd, 1H), 3.57(dd, 1H), 3.43(brs, 1H), 3.29(brs, 1H), 2.47(dd, 2H), 2.04-1.96(m, 3H), 1.77-1.68(m, 3H), 0.98(t, 3H) 188 (R)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H), 8.19(brs, 1H), (methoxymethyl)pyrrolidin- 7.48(d, 1H), 7.10(dd, 1H), 7.01-6.92(m, 2H), 6.45(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(s, 1H), 4.53(brs, 1H), 3.94(brs, 1H), 3.47(d, 1H), 1H-indol-6-amine 3.37(s, 3H), 3.31-3.16(m, 2H), 2.47(dd, 2H), 2.11- 2.00(m, 4H), 1.76-1.69(m, 2H), 0.99(t, 3H) 189 (S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.48(brs, 1H), 8.22(brs, 1H), (methoxymethyl)pyrrolidin- 7.48(d, 1H), 7.10(dd, 1H), 7.01-6.92(m, 2H), 6.46(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(s, 1H), 4.53(brs, 1H), 3.94(brs, 1H), 3.47(d, 1H), 1H-indol-6-amine 3.36(s, 3H), 3.31-3.16(m, 2H), 2.47(dd, 2H), 2.11- 2.00(m, 4H), 1.76-1.69(m, 2H), 0.99(t, 3H) 190 N-[4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 8.14(brs, 1H), 8.04(brs, 1H), yl)-6-propylpyrimidin-2-yl]- 7.49(d, 1H), 7.11-7.08(m, 3H), 6.47(dd, 1H), 5.67(s, 1H), 1H-indol-6-amine 4.28(brs, 1H), 3.59(brs, 1H), 3.42(brs, 1H), 2.47(dd, 2H), 2.12-1.98(m, 4H), 1.79-1.72(m, 2H), 1.27(dd, 3H), 0.99(t, 3H) 191 (S)-methyl 1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.56(brs, 1H), 8.31(brs, 1H), ylamino)-6-propylpyrimidin- 7.45(dd, 1H), 7.12(dd, 1H), 7.00(s, 1H), 6.45(dd, 1H), 4-yl]pyrrolidine-2- 5.74(brs, 1H), 4.75(brs, 1H), 3.63(s, 3H), 3.65-3.45(d, carboxylate 1H), 2.48(dd, 2H), 2.32-2.02(m, 4H), 1.75-1.70(m, 2H), 0.99(dd, 3H) 192 N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.68(brs, 1H), 8.10(brs, 1H), ylamino)-6-propylpyrimidin- 7.47(d, 1H), 7.11(s, 1H), 7.04(s, 1H), 6.46(s, 1H), 4-yl]pyrrolidin-3- 5.48(brs, 1H), 4.55(s, 1H), 3.82-3.44(m, 5H), 2.38- yl}acetamide 2.23(m, 3H), 2.03(s, 3H), 2.05-1.95(m, 1H), 1.75-1.68(m, 2H), 0.99(dd, 3H) 193 (S)-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 12.25(brs, 1H), 9.81-9.78(m, ylamino)-6-propylpyrimidin- 2H), 8.22(s, 1H), 7.37(d, 1H), 7.16(dd, 1H), 6.80(d, 1H), 4-yl]pyrrolidin-2-yl}methanol 6.37(s, 1H), 5.10(s, 1H), 4.70(brs, 1H), 4.50(brs, 1H), hydrochloride 4.06(d, 1H), 3.69(dd, 1H), 3.31(dd, 1H), 3.20-3.13(m, 1H), 2.30-1.98(m, 6H), 1.58-1.50(m, 2H), 0.93(t, 3H) 194 (S)-3-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s, 1H), 7.58(dd, 1H), (hydroxymethyl)pyrrolidin-1- 7.34(t, 1H), 7.24(d, 1H), 7.22(brs, 1H), 5.81(s, 1H), yl]-6-propylpyrimidin-2- 4.41(br, 1H), 3.73(m, 2H), 3.52(br, 1H), 3.39(m, 1H), ylamino}benzonitrile 2.51(t, 2H), 2.11-2.00(m, 3H), 1.88(br, 1H), 1.75(m, 2H), 0.99(t, 3H) 195 (S)-(1-{2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 10.30-10.13(br, 1H), 7.84(s, (methylthio)phenylamino]-6- 1H), 7.25(m, 2H), 6.98(s, 1H), 5.71(brs, 1H), 4.45(br, propylpyrimidin-4- 1H), 3.89(br, 1H), 3.68(br, 2H), 3.43(br, 1H), 2.70(br, yl}pyrrolidin-2-yl)methanol 2H), 2.49(s, 3H), 2.18(br, 1H), 2.08(m, 3H), 1.77(m, 2H), 1.00(m, 3H)

TABLE 1-21 Example Compound NMR Spectrum 196 (S)-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.87(s, 1H), 7.37(m, 2H), nitrophenylamino)-6- 7.34(br, 1H), 5.82(s, 1H), 4.44(br, 1H), 3.77(m, 2H), propylpyrimidin-4- 3.52(br, 1H), 3.39(br, 1H), 2.50(t, 2H), 2.07(m, 3H), yl]pyrrolidin-2-yl}methanol 1.94(m, 1H), 1.74(m, 2H), 1.00(t, 3H) 197 (S)-{1-[2-(1H-indol-5- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, 1H), 7.80(s, 1H), ylamino)-6-propylpyrimidin- 7.27(m, 3H), 7.13(m, 1H), 6.47(s, 1H), 5.69(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.59(m, 2H), 3.48(br, 1H), 3.38(br, 1H), 2.49(t, 2H), 1.97(m, 3H), 1.75(m, 3H), 1.99(t, 3H) 198 (S)-{1-[2-(1H- ¹H-NMR(400 MHz, CDCl₃) δ 8.84(s, 1H), 8.24(m, 2H), benzo[d]imidazol-5- 8.01(s, 1H), 7.56(d, 1H), 6.71(d, 1H), 6.06(s, 1H), ylamino)-6-propylpyrimidin- 4.57(br, 1H), 3.95(br, 1H), 3.72(m, 1H), 3.56(m, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.40(br, 1H), 2.63(m, 2H), 2.10(m, 3H), 1.82(m, 3H), 1.03(t, 3H) 199 (S)-(1-{6-propyl-2-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.42(brs, 1H), 7.59(d, 1H), (trifluoromethyl)-1H- 7.44(d, 1H), 7.38(d, 1H), 6.88(d, 1H), 6.84(s, 1H), benzo[d]imidazol-5- 5.93(brs, 1H), 3.76(br, 1H), 3.55(br, 1H), 3.35(s, 2H), ylamino]pyrimidin-4- 2.50(t, 2H), 2.11(m, 2H), 2.02(m, 2H), 1.77(m, 2H), yl}pyrrolidin-2-yl)methanol 1.02(t, 3H) 200 (S)-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 9.98(br, 1H), 7.45(br, 2H), methoxyphenylamino)-6- 6.84(d, 2H), 6.10-5.67(br, 1H), 4.38(br, 1H), 3.78(s, 3H), propylpyrimidin-4- 3.73(m, 2H), 3.59(br, 1H), 3.42(br, 1H), 2.52(m, 2H), yl]pyrrolidin-2-yl}methanol 2.15(br, 1H), 2.05(m, 3H), 1.75(m, 2H), 0.97(t, 3H) 201 (S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 10.45(br, 1H), 7.92(s, 1H), chlorophenylamino)-6- 7.36(br, 1H), 7.22(m, 1H), 7.03(m, 1H), 5.73(br, 1H), propylpyrimidin-4- 4.47(br, 1H), 4.13(m, 2H), 3.83(br, 1H), 3.43(br, 1H), yl]pyrrolidin-2-yl}methanol 2.51(m, 2H), 2.09(m, 4H), 1.75(m, 2H), 0.97(t, 3H) 202 (S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 10.17(br, 1H), 7.61(brs, 1H), methoxyphenylamino)-6- 7.21(m, 1H), 7.04(br, 1H), 6.63(m, 1H), 5.70(brs, 1H), propylpyrimidin-4- 4.42(br, 1H), 3.90(br, 1H), 3.81(s, 3H), 3.75(m, 2H), yl]pyrrolidin-2-yl}methanol 3.40(m, 1H), 2.53(m, 2H), 2.09(m, 4H), 1.76(m, 2H), 0.97(t, 3H) 203 (S)-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 10.62(br, 1H), 8.32(m, 1H), (trifluoromethyl)phenyl- 7.57(d, 1H), 7.41(brs, 1H), 7.33(m, 1H), 6.22-5.78(br, amino]pyrimidin- 1H), 4.50(br, 1H), 4.13(m, 1H), 3.93(m, 2H), 3.46(br, 4-yl}pyrrolidin- 1H), 2.53(br, 2H), 2.28-2.05(m, 4H), 1.77(m, 2H), 0.97(t, 2-yl)methanol 3H) 204 (S)-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(s, 1H), 7.09(d, 1H), methylphenylamino)-6- 6.95(d, 1H), 5.76(s, 1H), 4.33(br, 1H), 3.71-3.61(m, 2H), propylpyrimidin-4- 3.40(br, 1H), 3.39(br, 1H), 2.52(m, 2H), 2.30(s, 3H), yl]pyrrolidin-2-yl}methanol 2.11-2.00(m, 4H), 1.77(m, 2H), 1.00(t, 3H) 205 (S)-{1-[2-(5-methoxy-2- ¹H-NMR(400 MHz, CDCl₃) δ 9.31(br, 1H), 7.64(s, 1H), methylphenylamino)-6- 7.09(d, 1H), 6.62(m, 1H), 5.72(s, 1H), 4.27(br, 1H), propylpyrimidin-4- 3.82(s, 3H), 3.77(m, 1H), 3.46(m, 2H), 3.36(m, 1H), yl]pyrrolidin-2-yl}methanol 2.56(m, 2H), 2.31(s, 3H), 2.06-1.99(m, 4H), 1.80(m, 2H), 1.02(t, 3H)

TABLE 1-22 Example Compound NMR Spectrum 206 (S)-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 10.11(br, 1H), 7.91(d, 1H), methylphenylamino)-6- 7.23(br, 1H), 7.13(m, 1H), 6.14-5.73(br, 1H), 4.46(br, propylpyrimidin-4- 1H), 3.81(m, 2H), 3.63(br, 1H), 3.38(br, 1H), 2.52(m, yl]pyrrolidin-2-yl}methanol 2H), 2.32(s, 3H), 2.10(m, 4H), 1.78(m, 2H), 0.98(t, 3H) 207 (S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.15(s, 1H), 8.37(br, 1H), nitrophenylamino)-6- 7.83(d, 1H), 7.81(d, 1H), 7.41(t, 1H), 5.83(s, 1H), propylpyrimidin-4- 4.67(br, 1H), 4.13(m, 1H), 3.80(m, 1H), 3.56(br, 1H), yl]pyrrolidin-2-yl}methanol 3.42(br, 1H), 2.53(m, 2H), 2.17-2.05(m, 4H), 1.79(m, 2H), 1.00(t, 3H) 208 (S)-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.95(s, 1H), 7.85(br, 1H), nitrophenylamino)-6- 7.50(m, 1H), 7.16(t, 1H), 5.81(s, 1H), 4.49(br, 1H), propylpyrimidin-4- 4.45(br, 1H), 3.76(m, 2H), 3.53-3.39(m, 2H), 2.48(m, yl]pyrrolidin-2-yl}methanol 2H), 2.13(m, 3H), 1.75(m, 2H), 0.97(t, 3H) 209 (S)-{1-[6-propyl-2-(quinolin- ¹H-NMR(400 MHz, CDCl₃) δ 8.75(d, 1H), 8.38(d, 1H), 6-ylamino)pyrimidin-4- 8.09(d, 1H), 8.00(d, 1H), 7.72(dd, 1H), 7.33(m, 1H), yl]pyrrolidin-2-yl}methanol 5.81(s, 1H), 4.49(br, 1H), 3.75(m, 2H), 3.55(m, 1H), 3.42(m, 1H), 2.54(m, 2H), 2.07(m, 3H), 1.91(m, 1H), 1.78(m, 2H), 1.02(t, 3H) 210 (S)-{1-[2-(4-methyl-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.65(s, 1H), 7.56(s, 1H), nitrophenylamino)-6- 7.28(d, 1H), 6.01(s, 1H), 4.43-3.50(m, 5H), 2.53(m, 5H), propylpyrimidin-4- 2.12-2.02(m, 4H), 1.73(m, 2H), 1.00(t, 3H) yl]pyrrolidin-2-yl}methanol 211 (S)-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.77(brs, 1H), 7.34(d, 1H), (trifluoromethyl)phenylamino]- 6.85(d, 1H), 6.12(brs, 1H), 4.13(m, 1H), 3.93-3.50(m, 6-propylpyrimidin-4- 4H), 2.57(t, 2H), 2.09-1.98(m, 4H), 1.74(m, 2H), 1.03(t, yl}pyrrolidin-2-yl)methanol 3H) 212 (S)-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.82(s, 1H), 7.25(m, 1H), nitrophenylamino)-6- 6.82(brs, 1H), 6.74(d, 1H), 5.94(s, 2H), 5.74(s, 1H), propylpyrimidin-4- 4.52(s, 1H), 3.75(m, 1H), 3.63(m, 1H), 3.49(m, 1H), yl]pyrrolidin-2-yl}methanol 3.37(s, 1H), 2.47(t, 2H), 2.02(m, 3H), 1.90(m, 1H), 1.72(m, 2H), 0.98(t, 3H) 213 (S)-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.21(s, 1H), 7.45(d, 1H), (hydroxymethyl)pyrrolidin-1- 7.18(d, 1H), 6.97(brs, NH), 5.79(s, 1H), 4.41(s, 1H), yl]-6-propylpyrimidin-2- 3.71(m, 2H), 3.51(m, 1H), 3.38(s, 1H), 2.48(m, 5H), ylamino}-2- 2.02(m, 3H), 1.86(s, 1H), 1.70(m, 2H), 0.99(t, 3H) methylbenzonitrile 214 (S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.22(m, 1H), 7.58(m, 1H), (hydroxymethyl)pyrrolidin-1- 7.12(s, 1H), 7.07(t, 1H), 5.81(s, 1H), 4.39(s, 1H), 3.73(m, yl]-6-propylpyrimidin-2- 2H), 3.51(s, 1H), 3.38(s, 1H), 2.52(t, 2H), 2.02(m, 3H), ylamino}benzonitrile 1.84(s, 1H), 1.74(m, 2H), 0.99(t, 3H) 215 (S)-2-amino-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.83(s, 1H), 7.33(d, 1H), (hydroxymethyl)pyrrolidin-1- 6.76(d, 1H), 5.80(s, 1H), 4.42(m, 3H), 3.75(m, 3H), yl]-6-propylpyrimidin-2- 2.55(m, 2H), 2.07(m, 4H), 1.78(m, 2H), 1.00(t, 3H) ylamino}benzonitrile

TABLE 1-23 Example Compound NMR Spectrum 216 (S)-{1-[6-propyl-2-(quinolin- ¹H-NMR(400 MHz, CDCl₃) δ 8.94(s, 1H), 8.66(d, 1H), 3-ylamino)pyrimidin-4- 7.99(d, 1H), 7.72(d, 1H), 7.55-7.45(m, 2H), 7.25(br, 1H), yl]pyrrolidin-2-yl}methanol 5.80(s, 1H), 4.40(br, 1H), 3.75(m, 2H), 3.51(m, 1H), 3.40(m, 1H), 2.51(m, 2H), 2.04(m, 3H), 1.95(m, 1H), 1.77(m, 2H), 0.98(t, 3H) 217 (S)-{1-[2-(indolin-6- ¹H-NMR(400 MHz, CDC1₃) δ 7.21(s, 1H), 7.00(d, 1H), ylamino)-6-propylpyrimidin- 6.83(brs, 1H), 6.69(d, 1H), 5.69(s, 1H), 4.37(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.76(m, 1H), 3.62(m, 1H), 3.55(m, 1H), 3.46(m, 1H), 3.32(m, 1H), 2.96(t, 2H), 2.46(t, 2H), 2.00(m, 3H), 1.83(m, 1H), 1.69(m, 2H), 0.97(t, 3H) 218 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.19(d, 1H), 7.82-7.75(m, (cyclohexylamino)pyrrolidin- 1H), 7.61-7.54(m, 2H), 6.35(s, 1H), 4.23-3.74(m, 5H), 1-yl]-6-propylpyrimidin-2- 3.23(brs, 1H), 2.69(dd, 2H), 2.60(brs, 1H), 2.35-2.20(m, ylamino}benzonitrile 1H), 1.90(d, 2H), 1.85-1.72(m, 5H), 1.47-1.25(m, 5H), dihydrochloride 1.06(t, 3H) 219 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.25(brs, 1H), 7.79(brs, (isopropylamino)pyrrolidin- 1H), 7.60-7.52(m, 2H), 6.32(s, 1H), 4.21-3.75(m, 5H), 1-yl]-6-propylpyrimidin-2- 3.58-3.52(m, 1H), 2.68(dd, 2H), 2.60(brs, 1H), 2.32(brs, ylamino}benzonitrile 1H), 1.85-1.75(m, 2H), 1.42(dd, 6H), 1.06(t, 3H) dihydrochloride 220 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H), 7.82(s, 1H), (aminoethylamino)pyrrolidin- 7.60-7.54(m, 2H), 6.35(s, 1H), 4.18-3.75(m, 5H), 3.44- 1-yl]-6-propylpyrimidin-2- 3.40(m, 2H), 3.31-3.25(m, 2H), 2.69(dd, 2H), 2.67- ylamino}benzonitrile 2.49(m, 1H), 2.40-2.25(m, 1H), 1.83-1.76(m, 2H), 1.06(t, dihydrochloride 3H) 221 (S)-3-{4-[3-(piperidin-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.20(brs, 1H), 7.57(brs, ylamino)pyrrolidin-1-yl]-6- 1H), 7.38(dd, 1H), 7.22(d, 1H), 5.87(s, 1H), 4.15-3.31(m, propylpyrimidin-2- 7H), 3.01-2.94(m, 3H), 2.48(dd, 2H), 2.31-2.18(m, 2H), ylamino}benzonitrile 2.11(d, 1H), 1.91(brs, 1H), 1.75-1.68(m, 2H), 1.57- 1.46(m, 2H), 0.97(t, 3H) 222 (S)-3-{4-[3-(1-butylpiperidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.55-8.45(m, 1H), 7.32- 4-ylamino)pyrrolidin-1-yl]-6- 7.26(m, 1H), 7.39(dd, 1H), 7.23(d, 1H), 5.89(s, 1H), propylpyrimidin-2- 3.99-3.44(m, 6H), 2.99(d, 2H), 2.65(brs, 1H), 2.49(dd, ylamino}benzonitrile 2H), 2.39-2.28(m, 3H), 2.10-1.94(m, 4H), 1.85-1.69(m, 2H), 1.55-1.28(m, 6H), 1.00-0.87(m, 6H) 223 (S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.25(brs, 1H), 7.61(brs, 1H), cyanophenylamino)pyrimidin- 7.33-7.28(m, 2H), 7.17(d, 1H), 6.17(brs, 1H), 5.73(s, 4-yl]pyrrolidin-3- 1H), 4.58(brs, 1H), 3.92-3.33(m, 4H), 2.49(dd, 2H), 2.30- yl}acetamide 2.25(m, 1H), 2.04-2.00(m, 1H), 2.00(s, 3H), 1.69-1.61(m, 2H), 1.43-1.33(m, 2H), 0.94(t, 3H) 224 (S)-3-{4-butyl-6-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s, 1H), 7.58(dd, 1H), (hydroxymethyl)pyrrolidin-1- 7.34(dd, 1H), 7.22(d, 1H), 7.17(brs, 1H), 5.81 (s, 1H), yl]pyrimidin-2- 4.88-4.30(m, 2H), 3.75-3.69(m, 2H), 3.51(brs, 1H), ylamino}benzonitrile 3.38(brs, 1H), 2.53(dd, 2H), 2.11-2.00(m, 3H), 1.86(brs, 1H), 1.73-1.65(m, 2H), 1.45-1.37(m, 2H), 0.94(t, 3H) 225 (R)-3-[4-butyl-6-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.48(brs, 1H), 7.51(d, 1H), methylpyrrolidin-1- 7.33-7.25(m, 2H), 7.19(d, 1H), 5.74(s, 1H), 4.37-3.38(m, yl)pyrimidin-2- 3H), 2.49(dd, 2H), 2.08-2.01(m, 3H), 1.78-1.75(m, 1H), ylamino]benzonitrile 1.71-1.63(m, 2H), 1.44-1.36(m, 2H), 1.29(brs, 3H), 0.94(t, 3H)

TABLE 1-24 Example Compound NMR Spectrum 226 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.56(dd, 1H), (methylamino)pyrrolidin-1- 7.33-7.28(m, 2H), 7.17(d, 1H), 5.74(s, 1H), 3.78-3.16(m, yl]pyrimidin-2- 5H), 2.50(s, 3H), 2.48(dd, 2H), 2.22-2.17(m, 1H), ylamino}benzonitrile 1.91(brs, 1H), 1.70-1.62(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 227 (S)-tert-butyl 1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(brs, 1H), 7.61(brs, 1H), cyanophenylamino)pyrimidin- 7.33(dd, 1H), 7.20(d, 1H), 7.13(brs, 1H), 5.74(s, 1H), 4-yl]pyrrolidin-3- 4.80(brs, 1H), 4.34(brs, 1H), 3.82-3.33(m, 4H), 2.50(dd, ylcarbamate 2H), 2.29-2.23(m, 1H), 1.99(brs, 1H), 1.70-1.63(m, 2H), 1.46(s, 9H), 1.42-1.34(m, 2H), 0.95(t, 3H) 228 (S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H), 7.48(brs, 1H), cyano-4- 7.16(d, 1H), 7.06(brs, 1H), 6.01(brs, 1H), 5.71(s, 1H), methylphenylamino)pyrimidin- 4.60-4.56(m, 1H), 3.75-3.38(m, 4H), 2.48(dd, 2H), 4-yl]pyrrolidin-3- 2.45(s, 3H), 2.32-2.24(m, 1H), 2.04-2.00(m, 1H), 2.00(s, yl}acetamide 3H), 1.69-1.61(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 229 (S)-5-{4-butyl-6-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(dd, 1H), 7.45(dd, 1H), (hydroxymethyl)pyrrolidin-1- 7.18(d, 1H), 7.11(brs, 1H), 5.78(s, 1H), 4.40(brs, 1H), yl]pyrimidin-2-ylamino}-2- 3.74-3.69(m, 2H), 3.50(brs, 1H), 3.37(brs, 1H), 2.51(dd, methylbenzonitrile 2H), 2.47(s, 3H), 2.08-1.99(m, 3H), 1.86(brs, 1H), 1.72- 1.64(m, 2H), 1.42-1.37(m, 2H), 0.94(t, 3H) 230 (R)-5-[4-butyl-6-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.40(brs, 1H), methylpyrrolidin-1- 7.16(d, 1H), 7.03(brs, 1H), 5.72(s, 1H), 4.40-3.36(m, yl)pyrimidin-2-ylamino]-2- 3H), 2.48(dd, 2H), 2.47(s, 3H), 2.12-2.00(m, 3H), 1.77- methylbenzonitrile 1.75(m, 1H), 1.70-1.62(m, 2H), 1.44-1.36(m, 2H), 1.29(brs, 3H), 0.94(t, 3H) 231 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(d, 1H), 7.44(dd, 1H), (methylamino)pyrrolidin-1- 7.16(d, 1H), 7.11(brs, 1H), 5.72(s, 1H), 3.78-3.16(m, yl]pyrimidin-2-ylamino}-2- 5H), 2.50(s, 3H), 2.48(dd, 2H), 2.47(s, 3H), 2.22-2.16(m, methylbenzonitrile 1H), 1.90(brs, 1H), 1.70-1.62(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 232 (S)-tert-butyl 1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(brs, 1H), 7.50(brs, 1H), cyano-4- 7.17(d, 1H), 7.16(brs, 1H), 5.70(s, 1H), 4.90(brs, 1H), methylphenylamino)pyrimidin- 4.33(brs, 1H), 3.82-3.33(m, 4H), 2.49(dd, 2H), 2.47(s, 4-yl]pyrrolidin-3- 3H), 2.27-2.23(m, 1H), 1.99(brs, 1H), 1.69-1.62(m, 2H), ylcarbamate 1.46(s, 9H), 1.43-1.33(m, 2H), 0.95(t, 3H) 233 (S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H), 7.48(brs, 1H), 1-yl)-6-butylpyrimidin-2- 7.16(d, 1H), 7.06(brs, 1H), 6.01(brs, 1H), 5.71(s, 1H), ylamino]benzonitrile 4.60-4.56(m, 1H), 3.75-3.38(m, 4H), 2.48(dd, 2H), dihydrochloride 2.45(s, 3H), 2.32-2.24(m, 1H), 2.04-2.00(m, 1H), 2.00(s, 3H), 1.69-1.61(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 234 (S)-5-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H), 7.48(brs, 1H), 1-yl)-6-butylpyrimidin-2- 7.16(d, 1H), 7.06(brs, 1H), 6.01(brs, 1H), 5.71(s, 1H), ylamino]-2- 4.60-4.56(m, 1H), 3.75-3.38(m, 4H), 2.48(dd, 2H), methylbenzonitrile 2.45(s, 3H), 2.32-2.24(m, 1H), 2.04-2.00(m, 1H), 2.00(s, dihydrochloride 3H), 1.69-1.61(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 235 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.58(d, 1H), (isopropylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d, 1H), 7.17(brs, 1H), 5.73(s, 1H), 1-yl]pyrimidin-2- 3.90-3.38(m, 5H), 2.99-2.93(m, 1H), 2.50(dd, 2H), 2.28- ylamino}benzonitrile 2.21(m, 1H), 1.85(brs, 1H), 1.71-1.63(m, 2H), 1.44- 1.37(m, 2H), 1.11(t, 6H), 0.97(t, 3H)

TABLE 1-25 Example Compound NMR Spectrum 236 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(brs, 1H), 7.53(brs, 1H), (diethylamino)pyrrolidin-1- 7.32(dd, 1H), 7.21(d, 1H), 7.09(brs, 1H), 5.74(s, 1H), yl]pyrimidin-2- 4.04-3.35(m, 5H), 2.72(brs. 4H), 2.51(dd, 2H), 2.24(brs, ylamino}benzonitrile 1H), 1.93(brs, 1H), 1.71-1.64(m, 2H), 1.44-1.35(m, 2H), 1.05(t, 3H), 1.11(t, 6H), 0.97(t, 3H) 237 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.57(d, 1H), (cyclopropylmethylamino)pyrrolidin- 7.33(dd, 1H), 7.21(d, 1H), 7.11(brs, 1H), 5.74(s, 1H), 1-yl]pyrimidin-2- 3.91-3.14(m, 6H), 2.63-2.48(m. 4H), 2.26-2.18(m, 1H), ylamino}benzonitrile 1.90(brs, 1H), 1.71-1.63(m, 2H), 1.44-1.35(m, 2H), 1.25- 0.93(m, 4H), 0.53(dd, 2H), 0.15(d, 2H) 238 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.47(d, 1H), (isopropylamino)pyrrolidin- 7.17(d, 1H), 7.08(brs, 1H), 5.71(s, 1H), 3.90-3.05(m, 1-yl]pyrimidin-2-ylamino}-2- 5H), 2.99-2.93(m, 1H), 2.49(dd, 2H), 2.47(s, 3H), 2.28- methylbenzonitrile 2.20(m, 1H), 1.84(brs, 1H), 1.70-1.63(m, 2H), 1.44- 1.34(m, 2H), 1.11(dd, 6H), 0.97(t, 3H) 239 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.42(brs, 1H), (diethylamino)pyrrolidin-1- 7.16(d, 1H), 7.05(brs, 1H), 5.71(s, 1H), 4.04-3.18(m, yl]pyrimidin-2-ylamino}-2- 5H), 2.71(brs. 4H), 2.49(dd, 2H), 2.47(s, 3H), 2.23- methylbenzonitrile 1.92(m, 2H), 1.71-1.63(m, 2H), 1.44-1.35(m, 2H), 1.07(dd, 6H), H), 0.97(t, 3H) 240 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.45(d, 1H), (cyclopropylmethylamino)pyrrolidin- 7.17(d, 1H), 7.09(brs, 1H), 5.71(s, 1H), 3.90-3.05(m, 1-yl]pyrimidin-2- 5H), 2.56-2.48(m, 7H), 2.25-2.18(m, 1H), 1.89(brs, 1H), ylamino}-2- 1.70-1.63(m, 2H), 1.44-1.36(m, 2H), 1.25-0.93(m, 4H), methylbenzonitrile 0.53(dd, 2H), 0.15(d, 2H) 241 (S)-N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.89(brs, 1H), 8.10(brs, 1H), nitrophenylamino)-6- 7.35(s, 2H), 6.21(brs, 1H), 5.74(s, 1H), 4.63-4.59(m, propylpyrimidin-4- 1H), 4.10-3.38(m, 4H), 2.47(dd, 2H), 2.34-2.28(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.09-2.04(m, 1H), 2.03(s, 3H), 1.74-1.68(m, 2H), 0.97(t, 3H) 242 (S)-N-(1-{2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.78(s, 1H), 7.29(dd, 1H), (methylthio)phenylamino]-6- 7.18(dd, 1H), 7.01(brs, 1H), 6.84(d, 1H), 5.96(d, 1H), propylpyrimidin-4- 5.67(s, 1H), 4.59-4.56(m, 1H), 4.73-3.48(m, 4H), 2.68(s, yl}pyrrolidin-3-yl)acetamide 3H), 2.46(dd, 2H), 2.44-2.21(m, 1H), 2.06-2.00(m, 1H), 2.03(s, 3H), 1.76-1.66(m, 2H), 0.97(t, 3H) 243 (S)-N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.15(s, 1H), 7.49(d, 1H), ylamino)-6-propylpyrimidin- 7.11(dd, 1H), 7.00(d, 1H), 6.47(s, 1H), 5.95(brs, 1H), 4-yl]pyrrolidin-3- 5.62(s, 1H), 4.55(brs, 1H), 3.75-3.49(m, 4H), 2.45(dd, yl}acetamide 2H), 2.29-2.23(m, 1H), 2.06-2.00(m, 1H), 2.03(s, 3H), 1.75-1.66(m, 2H), 0.96(t, 3H) 244 (S)-N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(brs, 1H), 7.46(d, 1H), (trifluoromethyl)phenylamino]pyrimidin- 7.35(dd, 1H), 7.19(d, 2H), 5.88(d, 1H), 5.72(s, 1H), 4.62- 4-yl}pyrrolidin-3- 4.58(m, 1H), 3.75-3.49(m, 4H), 2.47(dd, 2H), 2.24- yl)acetamide 2.33(m, 1H), 2.06-2.00(m, 1H), 2.00(s, 3H), 1.76-1.67(m, 2H), 0.95(t, 3H) 245 (S)-N-{1-[2-(4-methyl-2-oxo- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(brs, 1H), 7.38(d, 1H), 2H-chromen-7-ylamino)-6- 7.35(dd, 1H), 6.99(brs, 1H), 6.98(d, 1H), 5.94(brs, 1H), propylpyrimidin-4- 5.72(s, 1H), 4.69(brs, 1H), 3.72-3.49(m, 4H), 2.45(dd, yl]pyrrolidin-3-yl}acetamide 2H), 2.33(s, 3H), 2.33-2.24(m, 1H), 2.06-2.00(m, 1H), 2.03(s, 3H), 1.75-1.67(m, 2H), 0.99(t, 3H)

TABLE 1-26 Example Compound NMR Spectrum 246 (S)-N{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.97(brs, 1H), 7.20(d, 1H), methylphenylamino)-6- 7.09(d, 1H), 7.00(brs, 1H), 6.15(d, 1H), 5.65(s, 1H), propylpyrimidin-4- 4.59(brs, 1H), 3.70-3.48(m, 4H), 2.45(dd, 2H), 2.30(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.28-2.23(m, 2H), 2.00(s, 3H), 1.72-1.66(m, 2H), 0.96(t, 3H) 247 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.27(brs, 1H), 7.76(dd, 1H), nitrophenylamino)-6- 7.45(brs, 1H), 7.37(brs, 1H), 7.24(brs, 1H), 5.89(s, 1H), propylpyrimidin-4- 5.76(s, 1H), 4.64-4.60(m, 1H), 3.86-3.32(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.48(dd, 2H), 2.36-2.28(m, 1H), 2.08-2.02(m, 1H), 2.02(s, 3H), 1.75-1.68(m, 2H), 0.98(t, 3H) 248 (S)-N-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.05(brs, 1H), 7.43(brs, 1H), nitrophenylamino)-6- 7.13(dd, 1H), 6.56(brs, 1H), 5.74(s, 1H), 4.64-4.61(m, propylpyrimidin-4- 1H), 3.83-3.43(m, 4H), 2.47(dd, 2H), 2.32(brs, 1H), 2.12- yl]pyrrolidin-3-yl}acetamide 2.05(m, 1H), 2.05(s, 3H), 1.75-1.67(m, 2H), 0.98(t, 3H) 249 (S)-N-{1-[2-(4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.93(brs, 1H), 7.82(brs, 1H), nitrophenylamino)-6- 7.33(d, 1H), 7.17(d, 1H), 6.38(brs, 1H), 5.69(s, 1H), propylpyrimidin-4- 4.62-4.58(m, 1H), 3.76-3.48(m, 4H), 2.51(s, 3H), yl]pyrrolidin-3-yl}acetamide 2.45(dd, 2H), 2.32-2.26(m, 1H), 2.08-2.02(m, 1H), 2.02(s, 3H), 1.73-1.67(m, 2H), 0.96(t, 3H) 250 (S)-benzyl 5-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.52(brs, 1H), 7.41-7.33(m, acetamidopyrrolidin-1-yl)-6- 5H), 7.18(d, 1H), 7.10(brs, 1H), 6.78(d, 1H), 5.93(s, 1H), propylpyrimidin-2-ylamino]- 5.64(s, 1H), 5.18(s, 2H), 4.55(brs, 1H), 3.82(s, 3H), 3.76- 2-methoxyphenylcarbamate 3.48(m, 4H), 2.45(dd, 2H), 2.26-2.20(m, 1H), 2.04- 1.96(m, 1H), 1.97(s, 3H), 1.73-1.66(m, 2H), 0.97(t, 3H) 251 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.21(brs, 1H), 7.61(brs, 2H), fluorophenylamino)-6- 7.09(dd, 1H), 6.07(brs, 1H), 5.74(s, 1H), 4.60(d, 1H), propylpyrimidin-4- 3.76-3.39(m, 4H), 2.48(dd, 2H), 2.33-2.28(m, 1H), 2.08- yl]pyrrolidin-3-yl}acetamide 2.02(m, 1H), 2.02(s, 3H), 1.76-1.67(m, 2H), 0.98(t, 3H) 252 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(brs, 1H), 7.49(brs, 2H), methylphenylamino)-6- 7.27(brs, 1H), 7.18(d, 1H), 5.99(d, 1H), 5.71(s, 1H), propylpyrimidin-4- 4.62-4.58(m, 1H), 3.75-3.41(m, 4H), 2.47(dd, 2H), yl]pyrrolidin-3-yl}acetamide 2.46(s, 3H), 2.32-2.27(m, 1H), 2.08-2.02(m, 1H), 2.01(s, 3H), 1.74-1.68(m, 2H), 0.97(t, 3H) 253 (S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.44(brs, 2H), (trifluoromethyl)phenylamino]- 7.08(dd, 1H), 5.91(brs, 1H), 5.72(s, 1H), 4.62-4.58(m, 6-propylpyrimidin-4- 1H), 3.75-3.39(m, 4H), 2.47(dd, 2H), 2.32-2.25(m, 1H), yl}pyrrolidin-3-yl)acetamide 2.08-2.01(m, 1H), 2.01(s, 3H), 1.76-1.66(m, 2H), 0.97(t, 3H) 254 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.97(brs, 1H), 7.24(brs, 1H), nitrophenylamino)-6- 6.98(brs, 1H), 6.73(d, 1H), 6.06(d, 1H), 5.92(brs, 2H), propylpyrimidin-4- 5.67(s, 1H), 4.61-4.57(m, 1H), 3.79-3.44(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.44(dd, 2H), 2.32-2.27(m, 1H), 2.08-2.01(m, 1H), 2.00(s, 3H), 1.75-1.65(m, 2H), 0.97(t, 3H) 255 (S)-N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.59(brs, 1H), 7.07(d, 1H), methylphenylamino)-6- 6.86(dd, 1H), 6.68(brs, 1H), 6.22(s, 1H), 5.68(s, 1H), propylpyrimidin-4- 4.58(s, 1H), 3.71-3.33(m, 5H), 2.47(dd, 2H), 2.30- yl]pyrrolidin-3-yl}acetamide 2.20(m, 2H), 2.27(s, 3H), 2.00(s, 3H), 1.73-1.68(m, 2H), 0.98(t, 3H)

TABLE 1-27 Example Compound NMR Spectrum 256 (S)-3-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.33(s, 1H), 7.82(d, 1H), acetamidopyrrolidin-1-yl)-6- 7.42(d, 1H), 7.35(t, 1H), 5.89(s, 1H), 4.50-4.40(m, 1H), propylpyrimidin-2- 3.90-3.30(m, 4H), 2.49(t, 2H), 2.30-2.20(m, 1H), 2.10- ylamino]benzamide 1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) 257 (S)-3-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.29(s, 1H), 7.80(s, 1H), acetamidopyrrolidin-1-yl)-6- 7.33(d, 2H), 5.87(s, 1H), 4.47(t, 1H), 3.90-3.30(m, 4H), propylpyrimidin-2-yl]amino}- 2.91 (s, 3H), 2.48(t, 2H), 2.35-2.20(m, 1H), 2.10-2.00(m, N-methylbenzamide 1H), 1.95(s, 3H), 1.72(q, 2H), 1.00(t, 3H) 258 (S)-N-[1-(2-{[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.03(t, 1H), 6.80-6.55(m, (aminomethyl)phenyl]amino}- 3H), 5.85(s, 1H), 4.50-4.35(m, 3H), 3.80-3.40(m, 4H), 6-propylpyrimidin-4- 2.47(t, 2H), 2.30-2.15(m, 1H), 2.05-1.95(m, 1H), 1.94(s, yl)pyrrolidin-3-yl]acetamide 3H), 1.68(q, 2H), 0.98(t, 3H) 259 (S)-3-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.35-7.20(m, 2H), 7.07(d, acetamidopyrrolidin-1-yl)-6- 1H), 6.28(brs, 1H), 4.55-4.35(m, 1H), 3.85-3.40(m, 4H), propylpyrimidin-2-yl]amino}- 2.51(t, 2H), 2.40-2.15(m, 1H), 2.15-1.90(m, 1H), 1.94(s, 4-chlorobenzamide 3H), 1.68(q, 2H), 0.95(t, 3H) 260 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.48(d, 1H), 7.44-7.40(m, cyanophenylamino)-6- 1H), 6.84(d, 1H), 6.13(d, 1H), 4.52-4.43(m, 1H), 3.86- propylpyrimidin-4- 3.44(m, 4H), 2.63-2.59(m, 2H), 2.33-2.25(m, 1H), 2.10- yl]pyrrolidin-3-yl}acetamide 2.02(m, 1H), 1.96(d, 3H), 1.78-1.73(m, 2H), 1.03(t, 3H) hydrochloride 261 (S)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.05-7.91(m, 2H), 7.33(dd, (trifluoromethyl)phenylamino]- 1H), 6.72(dd, 1H), 5.53(d, 1H), 4.72(brs, 1H), 4.19(brs, 6-propylpyrimidin-4- 2H), 4.03-3.50(m, 4H), 2.37-2.23(m, 4H), 2.11(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.68-1.53(m, 2H), 0.98(t, 3H) hydrochloride 262 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 7.15(d, 1H), 7.13(s, 1H), cyanophenylamino)-6- 6.67(s, 1H), 6.15(d, 1H), 4.54-4.47(m, 1H), 3.97-3.46(m, propylpyrimidin-4- 4H), 2.65-2.60(m, 2H), 2.41-2.30(m, 1H), 2.16-2.08(m, yl]pyrrolidin-3-yl}acetamide 1H), 1.97(s, 3H), 1.81-1.74(m, 2H), 1.04(t, 3H) hydrochloride 263 (S)-N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CD₃OD) δ 7.75(s, 1H), 7.54(d, 1H), ylamino)-6-propylpyrimidin- 7.26(s, 1H), 7.01(t, 1H), 6.45(s, 1H), 6.09(d, 1H), 4.47(d, 4-yl]pyrrolidin-3- 1H), 4.00-3.50(m, 4H), 2.59(q, 2H), 2.40-2.20(m, 1H), yl}acetamide hydrochloride 2.20-2.00(m, 1H), 1.96(s, 3H), 1.80-1.60(m, 2H), 1.03(t, 3H) 264 (S)-N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CD₃OD) δ 7.76(d, 1H), 7.35-7.15(m, methylphenylamino)-6- 2H), 6.21(d, 1H), 4.45(d, 1H), 3.90-3.50(m, 4H), 2.62(t, propylpyrimidin-4- 2H), 2.40-2.15(m, 4H), 2.15-1.85(m, 4H), 1.76(q, 2H), yl]pyrrolidin-3-yl}acetamide 1.05(t, 3H) hydrochloride 265 (S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(d, 1H), 7.77(brs, 1H), (trifluoromethyl)phenylamino]- 7.38(t, 1H), 6.26(d, 1H), 4.48(d, 1H), 3.90-3.45(m, 4H), 6-propylpyrimidin-4- 2.65(t, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), 1.95(s, yl}pyrrolidin-3-yl)acetamide 3H), 1.76(q, 2H), 1.05(t, 3H) hydrochloride

TABLE 1-28 Example Compound NMR Spectrum 266 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.05(brs, 1H), 6.94(t, 1H), fluorophenylamino)-6- 6.76(t, 1H), 6.13(d, 1H), 4.47(d, 1H), 4.00-3.40(m, 4H), propylpyrimidin-4- 2.65-2.50(m, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H), 1.75(q, 2H), 1.03(t, 3H) hydrochloride 267 (S)-N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.17(d, 1H), 7.80-7.70(m, (trifluoromethyl)phenylamino]pyrimidin- 1H), 7.59(t, 1H), 7.47(d, 1H), 6.26(d, 1H), 4.60-4.40(m, 4-yl}pyrrolidin-3-yl)acetamide 1H), 4.00-3.40(m, 4H), 2.66(t, 2H), 2.40-2.20(m, 1H), hydrochloride 2.20-2.00(m, 1H), 1.95(s, 3H), 1.78(q, 2H), 1.05(t, 3H) 268 (S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 7.29(d, 1H), 7.01(d, 1H), (trifluoromethyl)phenylamino]- 6.74(s, 1H), 6.21(d, 1H), 4.60-4.40(m, 1H), 4.00-3.40(m, 6-propylpyrimidin-4- 4H), 2.63(t, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), yl}pyrrolidin-3-yl)acetamide 1.95(s, 3H), 1.77(q, 2H), 1.04(t, 3H) hydrochloride 269 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.92(d, 1H), 8.04(d, 1H), nitrophenylamino)-6- 7.81(t, 1H), 7.63(t, 1H), 6.30(d, 1H), 4.60-4.45(m, 1H), propylpyrimidin-4- 4.10-3.40(m, 4H), 2.75-2.60(m, 2H), 2.45-2.25(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.20-2.00(m, 1H), 1.96(s, 3H), 1.90-1.70(m, 2H), 1.06(t, hydrochloride 3H) 270 (S)-N-(1-{2-[(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.90-7.75(m, 2H), 7.50- aminophenyl)amino]-6- 7.40(m, 2H), 6.26(d, 1H), 4.50-4.35(m, 1H), 4.00-3.40(m, propylpyrimidin-4- 4H), 2.66(q, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), yl}pyrrolidin-3-yl)acetamide 1.96(s, 3H), 1.90-1.70(m, 2H), 1.05(t, 3H) hydrochloride 271 (S)-N-(1-{2-[(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.28(d, 1H), 7.24(d, 1H), hydroxyphenyl)amino]-6- 7.01(s, 1H), 6.20(d, 1H), 4.49(d, 1H), 4.00-3.40(m, 4H), propylpyrimidin-4- 2.63(t, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), 1.96(s, yl}pyrrolidin-3-yl)acetamide 3H), 1.76(q, 2H), 1.03(t, 3H) hydrochloride 272 (S)-4-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.18(t, 1H), 6.98(d, 1H), acetamidopyrrolidin-1-yl)-6- 6.62(d, 1H), 6.17(d, 1H), 4.49(d, 1H), 4.00-3.40(m, 4H), propylpyrimidin-2-yl]amino}- 2.62(t, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), 1.95(s, 2-hydroxybenzoic acid 3H), 1.76(q, 2H), 1.04(1, 3H) hydrochloride 273 (S)-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H), 7.71(s, 1H), acetamidopyrrolidin-1-yl)-6- 6.93(d, 1H), 6.14(d, 1H), 4.47(d, 1H), 4.10-3.40(m, 4H), propylpyrimidin-2-yl]amino}- 2.62(t, 2H), 2.55-2.30(m, 1H), 2.30-2.00(m, 1H), 1.95(s, 2-hydroxybenzoic acid 3H), 1.04(q, 3H) hydrochloride 274 (S)-N-(1-{2-[(3-hydroxy-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.50(s, 1H), 7.10(brs, 1H), methylphenyl)amino]-6- 6.95(d, 1H), 6.70(brs, 1H), 6.61(s, 1H), 5.59(s, 1H), propylpyrimidin-4- 4.12(brs, 1H), 3.80-3.30(m, 4H), 2.44(t, 2H), 2.18(s, 3H), yl}pyrrolidin-3-yl)acetamide 2.15-1.95(m, 2H), 1.91(s, 3H), 1.66(q, 2H), 0.92(t, 3H) 275 (S)-N-(1-{2-[(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.96(s, 1H), 7.21(d, 1H), hydroxyphenyl)amino]-6- 6.92(d, 1H), 5.72(brs, 1H), 5.68(s, 1H), 4.12(d, 1H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.46(t, 2H), 2.35-2.20(m, 1H), 2.00- yl}pyrrolidin-3-yl)acetamide 1.90(m, 4H), 1.70(q, 2H), 0.97(t, 3H)

TABLE 1-29 Example Compound NMR Spectrum 276 (S)-N-(1-{2-[(4-hydroxy-3- ¹H-NMR(400 MHz, CDCl₃) δ 7.24(s, 1H), 6.85(brs, 1H), methylphenyl)amino]-6- 6.70(d, 1H), 6.26(d, 1H), 5.59(s, 1H), 4.52(brs, 1H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.43(t, 2H), 2.25-2.10(m, 1 + 3H), 2.00- yl}pyrrolidin-3-yl)acetamide 1.85(m, 1 + 3H), 1.67(q, 2H), 0.94(t, 3H) 277 (S)-N-(1-{2-[(3-fluoro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.75(d, 1H), 6.95(d, 1H), hydroxyphenyl)amino]-6- 6.89(t, 1H), 6.10(brs, 1H), 5.63(s, 1H), 4.59(brs, 1H), propylpyrimidin-4- 3.90-3.30(m, 4H), 2.45(t, 2H), 2.35-2.15(m, 1H), 2.10- yl}pyrrolidin-3-yl)acetamide 2.00(m, 1H), 1.99(s, 3H), 1.68(q, 2H), 0.96(t, 3H) 278 (S)-N-(1-{2-[(3-hydroxy-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.43(s, 1H), 7.10-7.00(m, methoxyphenyl)amino]-6- 1H), 6.78(d, 1H), 5.62(s, 1H), 4.59(s, 1H), 3.86(s, 3H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.45(t, 2H), 2.35-2.20(m, 1H), 2.10- yl}pyrrolidin-3-yl)acetamide 2.00(m, 1H), 2.01(s, 3H), 1.67(q, 2H), 0.96(t, 3H) 279 (S)-N-(1-{2-[(3-methoxy-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.56(s, 1H), 7.38(brs, 1H), methylphenyl)amino]-6- 7.00(d, 1H), 6.89(d, 1H), 5.78(brs, 1H), 5.65(s, 1H), propylpyrimidin-4- 4.59(brs, 1H), 3.83(s, 3H), 3.80-3.20(m, 4H), 2.46(t, 2H), yl}pyrrolidin-3-yl)acetamide 2.40-2.20(m, 2H), 2.16(s, 3H), 1.99(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 280 (S)-N-[1-(2-{[4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.37(d, 1H), (trifluoromethyl)phenyl]amino}- 7.21(brs, 1H), 7.16(d, 1H), 5.70(s, 1H), 4.60(brs, 1H), 6-propylpyrimidin-4- 3.85-3.20(m, 4H), 2.46(t, 2H), 2.41(s, 3H), 2.35-2.20(m, yl)pyrrolidin-3-yl]acetamide 1H), 2.15-2.00(m, 1H), 1.98(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 281 (S)-N-(1-{2-[(3,4- ¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 2H), 7.04(d, dimethylphenyl)amino]-6- 1H), 5.73(brs, 1H), 5.65(s, 1H), 4.62(brs, 1H), 3.85- propylpyrimidin-4- 3.20(m, 4H), 2.46(t, 2H), 2.40-2.25(m, 1H), 2.24(s, 3H), yl}pyrrolidin-3-yl)acetamide 2.21(s, 3H), 2.15-2.00(m, 1H), 2.00(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 282 (S)-N-(1-{2-[(3-fluoro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.73(d, 1H), 7.16(brs, 1H), methylphenyl)amino]-6- 7.10-7.00(m, 2H), 5.74(brs, 1H), 5.68(s, 1H), 4.61(brs, propylpyrimidin-4- 1H), 3.85-3.20(m, 4H), 2.47(t, 2H), 2.40-2.25(m, 1H), yl}pyrrolidin-3-yl)acetamide 2.21(s, 3H), 2.10-1.90(m, 4H), 1.71(q, 2H), 0.97(t, 3H) 283 (S)-N-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 11.06(d, 1H), 8.98(d, 1H), nitrophenylamino)-6- 7.55(d, 1H), 7.22(d, 1H), 6.78(s, 1H), 5.79(s, 1H), 4.68(s, propylpyrimidin-4- 1H), 4.05-3.59(m, 4H), 2.56-2.51(m, 2H), 2.40-2.21(m, yl]pyrrolidin-3-yl}acetamide 2H), 2.05(s, 3H), 1.82-1.76(m, 2H), 0.98-0.94(m, 3H) hydrochloride 284 (S)-N-{1-[2-(4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.78(d, 1H), 7.70-7.60(m, nitrophenylamino)-6- 1H), 7.38-7.34(m, 1H), 7.24-7.21(m, 1H), 5.73(d, 1H), propylpyrimidin-4- 4.73(brs, 1H), 4.08-3.70(m, 4H), 2.53(s, 3H), 2.46- yl]pyrrolidin-3-yl}acetamide 2.27(m, 4H), 2.11(s, 3H), 1.78-1.68(m, 2H), 0.98-0.94(m, hydrochloride 3H) 285 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 12.85(d, 1H), 10.66(d, 1H), methylphenylamino)-6- 8.10-7.88(m, 2H), 7.61-7.54(m, 1H), 7.29-7.24(m, 1H), propylpyrimidin-4- 5.73(s, 1H), 4.73(s, 1H), 4.06-3.73(m, 4H), 2.63(brs, yl]pyrrolidin-3-yl}acetamide 1H), 2.48(s, 3H), 2.44-2.28(m, 4H), 2.12(s, 3H), 1.73- hydrochloride 1.65(m, 2H), 0.97-0.93(m, 3H)

TABLE 1-30 Example Compound NMR Spectrum 286 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.66(s, 0.5H), 8.57(s, nitrophenylamino)-6- 0.5H), 7.46-7.42(m, 1H), 7.03(d, 1H), 6.18(s, 0.5H), propylpyrimidin-4- 6.14(s, 0.5H), 4.54-4.48(m, 1H), 3.92-3.60(m, 4H), 2.65- yl]pyrrolidin-3-yl}acetamide 2.60(m, 2H), 2.30-2.22(m, 1H), 2.13-2.05(m, 1H), 2.00(s, hydrochloride 1.5H), 1.99(s, 1.5H), 1.80-1.74(m, 2H), 1.07-1.02(m, 3H) 287 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(brs, 1H), 7.59(brs, 1H), cyanophenylamino)-6- 7.34(dd, 1H), 7.22(d, 1H), 6.98(brs, 1H), 5.76(s, 1H), propylpyrimidin-4- 5.66(d, 1H), 4.64-4.57(m, 1H), 3.77-3.35(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.48(dd, 2H), 2.36-2.29(m, 1H), 2.05-2.01(m, 1H), hydrochloride 2.01(s, 3H), 1.75-1.69(m, 2H), 0.98(t, 3H) 288 (S)-N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.66(s, 0.5H), 8.55(s, nitrophenylamino)-6- 0.5H), 7.73-7.64(m, 2H), 6.32(s, 0.5H), 6.28(s, 0.5H), propylpyrimidin-4- 4.53-4.50(m, 1H), 3.90-3.52(m, 4H), 2.70-2.65(m, 2H), yl]pyrrolidin-3-yl}acetamide 2.33-2.25(m, 1H), 2.15-2.07(m, 1H), 1.97(s, 3H), 1.82- hydrochloride 1.76(m, 2H), 1.07-1.03(m, 3H) 289 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.10(d, 1H), 6.97(dd, 1H), methoxyphenylamino)-6- 6.72(d, 1H), 5.95(brs, 1H), 5.62(s, 1H), 4.58(brs, 1H), propylpyrimidin-4- 3.82(s, 3H), 3.84-3.60(m, 6H), 2.44(dd, 2H), 2.28- yl]pyrrolidin-3-yl}acetamide 2.23(m, 1H), 2.02-1.95(m, 1H), 2.00(s, 3H), 1.74-1.65(m, 2H), 0.97(t, 3H) 290 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.24(d, 1H), 7.12-7.04(m, chlorophenylamino)-6- 2H), 6.93-6.89(m, 1H), 5.98(brs, 1H), 5.69(s, 1H), propylpyrimidin-4- 4.58(brs, 1H), 3.97(s, 2H), 3.75-3.36(m, 4H), 2.46(dd, yl]pyrrolidin-3-yl}acetamide 2H), 2.30-2.24(m, 1H), 2.06-1.96(m, 1H), 1.99(s, 3H), 1.74-1.68(m, 2H), 1.00(t, 3H) 291 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.25(d, 1H), 6.91-6.87(m, fluorophenylamino)-6- 2H), 5.72(d, 1H), 5.67(s, 1H), 5.60-4.55(m, 1H), 3.72(s, propylpyrimidin-4- 2H), 3.84-3.36(m, 4H), 2.46(dd, 2H), 2.31-2.26(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.06-1.96(m, 1H), 2.00(s, 3H), 1.75-1.66(m, 2H), 0.97(t, 3H) 292 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.14(d, 1H), 6.95-6.89(m, methylphenylamino)-6- 3H), 5.96(d, 1H), 5.63(s, 1H), 5.60-4.55(m, 1H), 3.84- propylpyrimidin-4- 3.36(m, 6H), 2.44(dd, 2H), 2.28-2.23(m, 1H), 2.12(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.02-1.95(m, 1H), 2.00(s, 3H), 1.72-1.67(m, 2H), 0.97(t, 3H) 293 N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.62 (s, 0.5H), 8.51(s, nitrophenylamino)-6- 0.5H), 7.41(brs, 1H), 6.99(d, 1H), 6.16(s, 1H), 4.49(d, propylpyrimidin-4- 1H), 3.83-3.44(m, 4H), 2.62(brs, 2 H), 2.34-2.27(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.11-2.01(m, 1H), 1.96(s, 3H), 1.78-1.74(m, 2H), 1.04(t, hydrochloride 3H) 294 N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.73(brs, NH), 8.32(s, 1H), cyanophenylamino)-6- 7.65(m, 1H), 7.33(m, 1H), 7.20(m, 1H), 6.14(brs, NH), propylpyrimidin-4- 5.70(s, 1H), 4.61(m, 1H), 3.76(m, 4H), 2.47(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.30(m, 1H), 2.02(m, 4H), 1.69(m, 2H), 0.98(t, 3H) 295 N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.18(s, 1H), 8.10(brs, NH), nitrophenylamino)-6- 7.76(d, 1H), 7.47(m, 1H), 7.34(m, 1H), 6.24(brs, NH), propylpyrimidin-4- 5.72(s, 1H), 4.63(m, 1H), 3.80-3.64(m, 4H), 2.47(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.33(m, 1H), 2.03(m, 4H), 1.71(m, 2H), 0.98(t, 3H)

TABLE 1-31 Example Compound NMR Spectrum 296 N-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.08(s, 1H), 8.10(brs, NH), nitrophenylamino)-6- 7.45(m, 1H), 7.13(m, 1H), 5.98(brs, NH), 5.75(s, 1H), propylpyrimidin-4- 4.62(m, 1H), 3.79-3.44(m, 4H), 2.49(t, 2H), 2.33(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.03(m, 4H), 1.70(m, 2H), 0.98(t, 3H) 297 N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.95(s, 1H), 7.81(brs, NH), nitrophenylamino)-6- 7.35(m, 2H), 5.94(brs, NH), 5.74(s, 1H), 4.60(m, 1H), propylpyrimidin-4- 3.76-3.40(m, 4H), 2.47(t, 2H), 2.31(m, 1H), 2.06(m, 4H), yl]pyrrolidin-3-yl}acetamide 1.70(m, 2H), 0.95(t, 3H) 298 N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.15(brs, NH), 7.51(s, 1H), methoxyphenylamino)-6- 7.16(t, 1H), 7.02(d, 1H), 6.72(brs, NH), 6.53(d, 1H), propylpyrimidin-4- 5.53(s, 1H), 4.63(m, 1H), 3.80(s, 3H), 3.70(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.39(t, 2H), 2.25(m, 1H), 2.04(m, 4H), 1.65(m, 2H), 0.95(t, 3H) 299 N-{1-[2-(5-methoxy-2- ¹H-NMR(400 MHz, CDCl₃) δ 7.91(s, 1H), 7.05(d, 1H), methylphenylamino)-6- 6.54(d, 1H), 5.63(s, 1H), 4.62(m, 1H), 3.78(s, 3H), 3.72- propylpyrimidin-4- 3.60(m, 4H), 2.46(4t, 2H), 2.30(s, 3H), 2.21(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.05(m, 4H), 1.67(m, 2H), 0.95(t, 3H) 300 N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, NH), 7.53(d, 2H), methoxyphenylamino)-6- 6.85(m, 2H + NH), 5.53(s, 1H), 4.66(m, 1H), 3.77(s, 3H), propylpyrimidin-4- 3.71-3.51(m, 4H), 2.39(t, 2H), 2.25(m, 1H), 2.05(m, 4H), yl]pyrrolidin-3-yl}acetamide 1.62(m, 2H), 0.94(t, 3H) 301 N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.60(brs, NH), 8.37(s, 1H), (trifluoromethyl)phenylamino]pyrimidin- 7.50(m, 1H), 7.37(t, 1H), 7.22(m, 1H), 6.85(brs, NH), 4-yl}pyrrolidin-3-yl)acetamide 5.65(s, 1H), 4.66(m, 1H), 3.75-3.60(m, 4H), 2.39(t, 2H), 2.26(m, 1H), 2.11(m, 1H), 2.04(s, 3H), 1.66(m, 2H), 0.94(t, 3H) 302 N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.42(brs, NH), 7.91(s, 1H), chlorophenylamino)-6- 7.33(d, 1H), 7.18(t, 1H), 6.94(d, 1H), 6.74(brs, NH), propylpyrimidin-4- 5.58(s, 1H), 4.66(m, 1H), 3.73-3.70(m, 4H), 2.42(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.29(m, 1H), 2.11(m, 1H), 2.06(s, 3H), 1.64(m, 2H), 0.96(t, 3H) 303 N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.43(s, 1H), 7.06(d, 1H), methylphenylamino)-6- 6.90(d, 1H), 6.31(brs, NH), 5.68(s, 1H), 4.62(m, 1H), propylpyrimidin-4- 3.73-3.44(m, 4H), 2.48(t, 2H), 2.31(s, 3H), 2.24(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.01(m, 4H), 1.70(m, 2H), 0.98(t, 3H) 304 N-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.52(brs, NH), 7.86(s, 1H), methylphenylamino)-6- 7.27(m, 1H), 7.10(d, 1H), 7.05(brs, NH), 5.52(s, 1H), propylpyrimidin-4- 4.65(m, 1H), 3.70(m, 4H), 2.37(m, 2H), 2.28(s, 3H), yl]pyrrolidin-3-yl}acetamide 2.26(m, 1H), 2.13(m, 1H), 2.07(s, 3H), 1.63(m, 2H), 0.95(t, 3H) 305 N-(1-{2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.13(brs. NH), 7.73(s, 1H), (methylthio)phenylamino]-6- 7.30(d, 1H), 7.18(t, 1H), 6.85(d, 1H), 6.57(brs, NH), propylpyrimidin-4- 5.57(s, 1H), 4.63(m, 1H), 3.72(m, 4H), 2.48(s, 3H), yl}pyrrolidin-3-yl)acetamide 2.39(t, 2H), 2.26(m, 1H), 2.04(m, 4H), 1.64(m, 2H), 0.94(t, 3H)

TABLE 1-32 Example Compound NMR Spectrum 306 N-{1-[2-(1H-indol-5- ¹H-NMR(400 MHz, CDCl₃) δ 8.11(s, NH), 7.98(s, 1H), ylamino)-6-propylpyrimidin- 7.37(d, 1H), 7.35(m, 1H), 7.30(m, 1H), 7.17(m, 1H), 4-yl]pyrrolidin-3- 6.99(brs, NH), 6.49(s, 1H), 5.75(brs, NH), 5.64(s, 1H), yl}acetamide 4.60(m, 1H), 3.81-3.43(m, 4H), 2.48(t, 2H), 2.25(m, 1H), 1.98(m, 4H), 1.71(m, 2H), 0.98(t, 3H) 307 N-(1-{6-propyl-2-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.60(brs, 1H), 7.64(s, 1H), (trifluoromethyl)-1H- 7.53(brs, 1H), 7.10(s, 1H), 6.12(s, 1H), 5.68(s, 1H), benzo[d]imidazol-5- 4.47(m, 1H), 3.92-3.54(m, 4H), 2.48(m, 2H), 2.27(m, ylamino]pyrimidin-4- 1H), 2.01(m, 4H), 1.71(m, 2H), 0.98(t, 3H) yl}pyrrolidin-3-yl)acetamide 308 N-{1-[6-propyl-2-(quinolin-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.67(s, 1H), 8.28(s, 1H), ylamino)pyrimidin-4- 7.91(m, 2H), 7.64(m, 1H), 7.31(brs, NH), 7.24(m, 1H), yl]pyrrolidin-3-yl}acetamide 6.80(brs, NH), 5.65(s, 1H), 4.63(m, 1H), 3.71-3.54(m, 4H), 2.50(t, 2H), 2.23(m, 1H), 2.04(m, 4H), 1.70(m, 2H), 0.98(t, 3H) 309 N-{1-[2-(4-methyl-2-oxo-2H- ¹H-NMR(400 MHz, CD₃OD) δ 8.22(m, 1H), 7.65(d, 1H), chromen-7-ylamino)-6- 7.46(m, 1H), 6.13(s, 1H), 5.93(s, 1H), 4.49(m, 1H), 3.80- propylpyrimidin-4- 3.55(m, 4H), 2.53(t, 2H), 2.49(s, 3H), 2.29(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.10(m, 1H), 1.96(s, 3H), 1.73(m, 2H), 0.99(t, 3H) 310 N-{1-[6-propyl-2-(quinolin-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.98(s, 1H), 8.58(s, 1H), ylamino)pyrimidin-4- 7.97(d, 1H), 7.66(m, 2H), 7.52-7.46(m, 2H), 5.80(brs, yl]pyrrolidin-3-yl}acetamide NH), 5.53(s, 1H), 4.63(m, 1H), 3.71-3.57(m, 4H), 2.44(t, 2H), 2.27(m, 1H), 2.05(m, 4H), 1.68(m, 2H), 0.97(t, 3H) 311 N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.33(m, 1H), 7.59-7.50(d, cyanophenylamino)-6- 1H), 7.39(m, 1H), 6.84(d, 1H), 6.13(d, 1H), 4.49(m, 1H), propylpyrimidin-4- 3.86(m, 1H), 3.68(m, 2H), 3.45(m, 1H), 2.61(m, 2H), yl]pyrrolidin-3-yl}acetamide 2.27(m, 1H), 2.04(m, 1H), 1.94(s, 3H), 1.73(m, 2H), hydrochloride 1.05(m, 3H) 312 N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.04(m, 1H), 6.96(t, 1H), fluorophenylamino)-6- 6.75(m, 1H), 6.17(d, 1H), 4.51-4.43(m, 1H), 3.92-3.40(m, propylpyrimidin-4- 4H), 2.60(m, 2H), 2.37(m, 1H), 2.10(m, 1H), 1.95(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.75(q, 2H), 1.03(t, 3H) hydrochloride 313 (R)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.91(s, 1H), 7.54(d, 1H), nitrophenyl)-4-(2- 7.44(d, 1H), 5.83(brs, 1H), 4.56-3.44(m, 3H), 2.62(dd, methylpyrrolidin-1-yl)-6- 2H), 2.26-2.03(m, 3H), 1.88-1.79(m, 3H), 1.31(brs, 3H), propylpyrimidin-2-amine 1.02(t, 3H) 314 (R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 8.57(s, 1H), 7.80(s, 1H), yl)-N-[3-(methylthio)phenyl]- 7.34(dd, 1H), 7.20(dd, 1H), 6.89(d, 1H), 5.70(brs, 1H), 6-propylpyrimidin-2-ylamine 4.56-3.37(m, 3H), 2.53(dd, 2H), 2.48(s, 3H), 2.10- 2.04(m, 3H), 1.82-1.73(m, 3H), 1.28(d, 3H), 0.99(t, 3H) 315 (R)-N-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 9.16(brs, 1H), 8.96(brs, 1H), methylpyrrolidin-1-yl)-6- 8.02(s, 1H), 7.44(d, 1H), 7.13-7.11(m, 1H), 6.41(s, 1H), propylpyrimidin-2-yl]-1H- 5.46(s, 1H), 4.56-3.29(m, 3H), 2.39(dd, 2H), 2.10- indol-6-amine 2.04(m, 3H), 1.72-1.66(m, 3H), 1.21(brs, 3H), 0.93(t, 3H)

TABLE 1-33 Example Compound NMR Spectrum 316 (R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 9.03(brs, 1H), 8.48(s, 1H), yl)-6-propyl-N-[3- 7.51(d, 1H), 7.38(dd, 1H), 7.26(d, 1H), 5.75(s, 1H), 4.48- (trifluoromethyl)phenyl]pyrimidin- 3.43(m, 3H), 2.55(dd, 2H), 2.18-2.04(m, 3H), 1.84- 2-amine 1.74(m, 3H), 1.28(d, 3H), 1.00(t, 3H) 317 (R)-4-methyl-7-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(s, 1H), 7.69(brs, 1H), methylpyrrolidin-1-yl)-6- 7.46(d, 1H), 7.21(dd, 1H), 6.11(s, 1H), 5.77(s, 1H), 4.14- propylpyrimidin-2-ylamino]- 3.32(m, 3H), 2.50(dd, 2H), 2.39(s, 3H), 2.12-2.03(m, 2H-chromen-2-one 3H), 1.79-1.71(m, 3H), 1.30(brs, 3H), 1.00(t, 3H) 318 (R)-N-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.78(brs, 1H), 8.06(s, 1H), methylphenyl)-4-(2- 7.23(d, 1H), 7.11(d, 1H), 5.70(s, 1H), 4.52-3.35(m, 3H), methylpyrrolidin-1-yl)-6- 2.53(dd, 2H), 2.31(s, 3H), 2.12-2.03(m, 3H), 1.81- propylpyrimidin-2-amine 1.75(m, 3H), 1.30(brs, 3H), 1.00(t, 3H) 319 (R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 9.23(dd, 1H), 7.85(dd, 1H), yl)-N-(3-nitrophenyl)-6- 7.58(dd, 1H), 7.41(dd, 1H), 5.78(s, 1H), 4.67-3.40(m, propylpyrimidin-2-ylamine 3H), 2.56(dd, 2H), 2.12-2.03(m, 3H), 1.85-1.75(m, 3H), 1.32(brs, 3H), 1.01(t, 3H) 320 (R)-N-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.08(d, 1H), 7.61-7.57(m, nitrophenyl)-4-(2- 1H), 7.22(dd, 1H), 5.81(s, 1H), 4.63-3.44(m, 3H), methylpyrrolidin-1-yl)-6- 2.60(dd, 2H), 2.22-2.08(m, 3H), 1.88-1.78(m, 3H), propylpyrimidin-2-amine 1.32(brs, 3H), 1.02(t, 3H) 321 (R)-N-(4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.39(brs, 1H), 8.99(d, 1H), nitrophenyl)-4-(2- 7.43(dd, 1H), 7.23(d, 1H), 5.77(s, 1H), 4.60-3.38(m, 3H), methylpyrrolidin-1-yl)-6- 2.56(dd, 2H), 2.55(s, 3H), 2.17-2.03(m, 3H), 1.85- propylpyrimidin-2-amine 1.77(m, 3H), 1.30(brs, 3H), 1.01(t, 3H) 322 (R)-N-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.02(brs, 1H), 8.42(dd, 1H), (trifluoromethyl)phenyl]-4- 7.53-7.50(m, 1H), 7.11(dd, 1H), 5.75(s, 1H), 4.47- (2-methylpyrrolidin-1-yl)-6- 3.34(m, 3H), 2.55(dd, 2H), 2.55(s, 3H), 2.17-2.03(m, propylpyrimidin-2-ylamine 3H), 1.83-1.76(m, 3H), 1.26(d, 3H), 1.00(t, 3H) 323 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.72(brs, 1H), 8.14(s, 1H), methylpyrrolidin-1-yl)-6- 7.30-7.27(m, 1H), 6.72(d, 1H), 5.68(s, 1H), 4.33-3.38(m, propylpyrimidin-2-yl]-3- 3H), 4.09(s, 2H), 2.52(dd, 2H), 2.17-2.03(m, 3H), 1.82- (trifluoromethyl)benzene- 1.72(m, 3H), 1.23(d, 3H), 0.99(t, 3H) 1,4-diamine 324 (R)-benzyl 2-methoxy-5-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(brs, 1H), 7.46-7.26(m, (2-methylpyrrolidin-1-yl)-6- 6H), 6.78(d, 1H), 5.65(s, 1H), 5.19(s, 2H), 3.81(s, 3H), propylpyrimidin-2- 4.44-3.34(m, 3H), 2.46(dd, 2H), 2.10-1.95(m, 3H), 1.76- ylamino]phenylcarbamate 1.68(m, 3H), 1.21(d, 3H), 0.98(t, 3H) 325 (R)-2-fluoro-5-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.60(brs, 1H), methylpyrrolidin-1-yl)-6- 7.12(dd, 1H), 5.77(s, 1H), 4.45-3.36(m, 3H), 2.54(dd, propylpyrimidin-2- 2H), 2.18-2.03(m, 3H), 1.83-1.73(m, 3H), 1.31(brs, 3H), ylamino]benzonitrile 1.00(t, 3H)

TABLE 1-34 Example Compound NMR Spectrum 326 (R)-2-methyl-5-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.91(brs, 1H), 8.37(brs, 1H), methylpyrrolidin-1-yl)-6- 7.48(d, 1H), 7.21(d, 1H), 5.75(s, 1H), 4.45-3.41(m, 3H), propylpyrimidin-2- 2.54(dd, 2H), 2.49(s, 3H), 2.18-2.03(m, 3H), 1.83- ylamino]benzonitrile 1.75(m, 3H), 1.32(brs, 3H), 1.00(t, 3H) 327 (R)-2-amino-5-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.12(brs, 1H), 7.31(d, 1H), methylpyrrolidin-1-yl)-6- 7.16(brs, 1H), 6.69(d, 1H), 4.20(s, 2H), 4.45-3.54(m, propylpyrimidin-2- 3H), 2.45(dd, 2H), 2.09-2.01(m, 3H), 1.76-1.66(m, 3H), ylamino]benzonitrile 1.26(d, 3H), 0.98(t, 3H) 328 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.97(s, 1H), 8.87(brs, 1H), methylpyrrolidin-1-yl)-6- 7.29(dd, 1H), 6.73(d, 1H), 6.23(s, 2H), 5.71(s, 1H), 4.63- propylpyrimidin-2-yl]-3- 3.33(m, 3H), 2.53(dd, 2H), 2.09-2.01(m, 3H), 1.82- nitrobenzene-1,4-diamine 1.73(m, 3H), 1.28(brs, 3H), 0.99(t, 3H) 329 (R)-1-{6-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.65(brs, 1H), 7.44(brs, 1H), methylpyrrolidin-1-yl)-6- 7.07(d, 1H), 5.68(s, 1H), 4.04(dd, 2H), 4.63-3.33(m, 3H), propylpyrimidin-2- 3.13(dd, 2H), 2.50(dd, 2H), 2.20(s, 3H), 2.10-2.01(m, ylamino]indolin-1- 3H), 1.79-1.73(m, 3H), 1.22(d, 3H), 0.99(t, 3H) yl}ethanone 330 (R)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.69(s, 1H), 7.04(d, 1H), methylphenyl)-4-(2- 6.84(dd, 1H), 6.68(brs, 1H), 5.71(s, 1H), 4.46-3.27(m, methylpyrrolidin-1-yl)-6- 3H), 2.46(dd, 2H), 2.28(s, 3H), 2.20-2.03(m, 3H), 1.75- propylpyrimidin-2-amine 1.67(m, 3H), 1.28(brs, 3H), 0.99(t, 3H) 331 (R)-4-methoxy-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.18(s, 1H), 6.96(dd, 1H), methylpyrrolidin-1-yl)-6- 6.71(d, 1H), 5.64(s, 1H), 4.56-3.33(m, 3H), 3.82(s, 3H), propylpyrimidin-2- 3.76(s, 2H), 2.46(dd, 2H), 2.09-1.99(m, 3H), 1.77- yl]benzene-1,3-diamine 1.66(m, 3H), 1.26(d, 3H), 0.98(t, 3H) 332 (R)-4-chloro-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.37(s, 1H), 7.10(d, 1H), methylpyrrolidin-1-yl)-6- 6.90(dd, 1H), 5.68(s, 1H), 4.56-3.33(m, 3H), 3.96(s, 2H), propylpyrimidin-2- 2.45(dd, 2H), 2.07-2.00(m, 3H), 1.76-1.66(m, 3H), yl]benzene-1,3-diamine 1.26(d, 3H), 0.99(t, 3H) 333 (R)-4-fluoro-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.31(d, 1H), 6.97(s, 1H), methylpyrrolidin-1-yl)-6- 6.87(d, 2H), 5.67(s, 1H), 4.56-3.33(m, 3H), 3.67(s, 2H), propylpyrimidin-2- 2.45(dd, 2H), 2.12-1.98(m, 3H), 1.75-1.68(m, 3H), yl]benzene-1,3-diamine 1.26(d, 3H), 0.98(t, 3H) 334 (R)-4-methyl-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 9.56(s, 1H), 7.08(d, 1H), methylpyrrolidin-1-yl)-6- 7.02(s, 1H), 6.96(d, 3H), 5.66(s, 1H), 4.55-3.36(m, 5H), propylpyrimidin-2- 2.56(dd, 2H), 2.15-2.07(m, 2H), 2.12(s, 3H), 1.85- yl]benzene-1,3-diamine 1.76(m, 2H), 1.29(brs, 3H), 1.00(t, 3H) 335 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz, CD₃OD) δ 7.81-7.70(m, 2H), 7.49(d, hydroxyethylamino)pyrrolidin- 1H), 7.30(d, 1H), 6.30(s, 1H), 4.21-3.77(m, 9H), 2.69- 1-yl]-6-propylpyrimidin-2- 2.30(m, 4H), 1.82(brs, 2H), 1.05(t, 3H) ylamino}benzonitrile dihydrochloride

TABLE 1-35 Example Compound NMR Spectrum 336 (S)-5-{4-butyl-6-[2- ¹H-NMR(400 MHz, CD₃OD) δ 7.99(d, 1H), 7.70(d, 1H), (hydroxymethyl)pyrrolidin-1- 7.44(d, 1H), 6.31(d, 1H), 4.28(d, 1H), 3.84-3.56(m, 4H), yl]pyrimidin-2-ylamino}-2- 2.66(dd, 2H), 2.51(s, 3H), 2.12-2.02(m, 4H), 1.76- methylbenzonitrile 1.68(m, 2H), 1.48-1.43(m, 2H), 1.03(t, 3H) hydrochloride 337 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.86(brs, 1H), 7.42(d, 1H), nitrophenylamino)-6- 6.90(d, 1H), 5.83(s, 1H), 4.48(s, 1H), 3.78-3.40(m, 4H), butylpyrimidin-4- 2.49(dd, 2H), 2.28-2.23(m, 1H), 2.04-1.99(m, 1H), yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H), 1.71-1.64(m, 2H), 1.45-1.35(m, 2H), 0.98(t, 3H) 338 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.06(brs, 1H), 7.34(d, 1H), (methylamino)pyrrolidin-1- 6.90(d, 1H), 5.85(s, 1H), 3.96-3.44(m, 5H), 2.64(s, 3H), yl]pyrimidin-2-yl}-3- 2.49(dd, 2H), 2.39(brs, 1H), 2.08(brs, 1H), 1.71-1.64(m, nitrobenzene-1,4-diamine 2H), 1.44-1.36(m, 2H), 0.96(t, 3H) 339 (S)-3-(4-{3-[(1H-pyrrol-2- ¹H-NMR(400 MHz, CD₃OD) δ 10.59-10.51(m, 1H), yl)methylamino]pyrrolidin-1- 8.12(s, 1H), 7.83(d, 1H), 7.60-7.56(m, 2H), 6.87-6.83(m, yl}-6-propylpyrimidin-2- 1H), 6.36-6.30(m, 2H), 6.16-6.12(m, 1H), 4.36-4.33(m, ylamino)benzonitrile 2H), 4.12-3.75(m, 5H), 2.71-2.58(m, 3H), 2.41-2.30(m, dihydrochloride 1H), 1.83-1.77(m, 2H), 1.06(dd, 3H) 340 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 10.71(s, 1H), 8.96(d, 1H), (methoxymethyl)pyrrolidin- 7.38(s, 1H), 6.85(s, 1H), 6.15-6.13(m, 2H), 5.89(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 4.68-3.43(m, 5H), 3.31(d, 3H), 2.62(brs, 2H), 2.33- 3-nitrobenzene-1,4-diamine 2.05(m, 4H), 1.88-1.84(m, 2H), 1.00(m, 3H) hydrochloride 341 (S)-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 13.50(s, 1H), 13.18(s, 1H), nitrophenylamino)-6- 11.25(s, 1H), 11.04(s, 1H), 9.05(m, 1H), 8.97(m, 1H), propylpyrimidin-4- 7.63(m, 2H), 7.26(m, 2H), 6.34(s, 1H), 5.84(s, 1H), yl]pyrrolidin-2-yl}methanol 4.62(m, 1H), 4.20(m, 1H), 3.83(m, 2H), 3.81(m, 3H), hydrochloride 3.76(m, 3H), 3.47(m, 2H), 2.65(m, 3H), 2.31(m, 3H), 2.13(m, 4H), 1.86(m, 4H), 1.01(m, 6H) 342 (S)-N¹-[4-(3- ¹H-NMR(400MHz, CD₃OD) δ 7.97(d, 1H), 7.75(d, 1H), aminopyrrolidin-1-yl)-6- 7.30(d, 1H), 6.37(s, 1H), 4.17-3.75(m, 5H), 2.71(t, 2H), propylpyrimidin-2-yl]-5- 2.58(m, 1H), 2.33(m, 1H), 1.82(m, 2H), 1.06(t, 3H) (trifluoromethyl)benzene- 1,3-diamine dihydrochloride 343 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.63(br, 1H), 7.60(s, 1H), aminopyrrolidin-1-yl)-6- 7.38(m, 1H), 6.31(d, 1H), 4.15-3.75(m, 5H), 2.68(t, 2H), propylpyrimidin-2-yl]-3- 2.53(m, 1H), 2.43(d, 3H), 2.29(m, 1H), 1.82(m, 2H), methylbenzene-1,4-diamine 1.07(t, 3H) dihydrochloride 344 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.59(d, 1H), 7.75-7.64(m, yl)-N-(4-chloro-3- 2H), 7.41(d, 1H), 6.57(d, 1H), 4.11-3.78(m, 5H), nitrophenyl)-6- 2.72(m, 2H), 2.65(m, 1H), 2.04(m, 1H), 1.78(m, 2H), propylpyrimidin-2-amine 1.06(m, 3H) dihydrochloride 345 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.51(d, 1H), 7.33(m, 2H), yl)-N-[3-(methylthio)phenyl]- 7.01(m, 1H), 6.28(brs, 1H), 4.15-3.75(m, 5H), 2.67(m, 6-propylpyrimidin-2-amine 2H), 2.56(m, 1H), 2.50(s, 3H), 2.24(m, 1H), 1.79(m, 2H), dihydrochloride 1.29(m, 3H)

TABLE 1-36 Example Compound NMR Spectrum 346 (S)-N-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 7.67(d, 1H), 7.56(d, 1H), 1-yl)-6-propylpyrimidin-2-yl]- 7.28(s, 2H), 7.05(d, 1H), 6.17(d, 1H), 4.14-3.71(m, 5H), 1H-indol-6-amine 2.62(m, 2H), 2.57(m, 1H), 2.29(m, 1H), 1.78(m, 2H), dihydrochloride 1.04(t, 3H) 347 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.05(d, 1H), 7.81- yl)-6-propyl-N-[3- 7.30(dd, 1H), 7.62(m, 1H), 7.50(m, 1H), 6.34(d, 1H), (trifluoromethyl)phenyl]pyrimidin- 4.17-3.74(m, 5H), 2.70(m, 2H), 2.57(m, 1H), 2.25(m, 2-amine dihydrochloride 1H), 1.83(m, 2H), 1.06(t, 3H) 348 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.77-7.67(d, 1H), 7.29(d, yl)-N-(5-chloro-2- 1H), 7.21(m, 1H), 6.28(d, 1H), 4.11-3.70(m, 5H), 2.67(m, methylphenyl)-6- 2H), 2.55(m, 1H), 2.30(d, 3H), 2.20(m, 1H), 1.79(m, 2H), propylpyrimidin-2-amine 1.05(t, 3H) dihydrochloride 349 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.78-7.71(d, 1H), 7.37- yl)-N-(3-chloro-4- 7.30(m, 2H), 6.28(s, 1H), 4.08-3.81(m, 5H), 2.66(m, 2H), methylphenyl)-6- 2.52(m, 1H), 2.35(s, 3H), 2.20(m, 1H), 1.80(m, 2H), propylpyrimidin-2-amine 1.05(t, 3H) dihydrochloride 350 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.94(d, 1H), 8.05(m, 1H), yl)-N-(3-nitrophenyl)-6- 7.82(m, 1H), 7.64(m, 1H), 6.60(d, 1H), 4.16-3.76(m, 5H), propylpyrimidin-2-amine 2.71(m, 2H), 2.55(m, 1H), 2.30(m, 1H), 1.84(m, 2H), dihydrochloride 1.07(t, 3H) 351 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.64(d, 1H), 7.64(m, 1H), yl)-N-(4-methyl-3- 7.47(m, 1H), 6.64(d, 1H), 4.16-3.71(m, 5H), 2.70(m, 2H), nitrophenyl)-6- 2.56(s, 3H), 2.54(m, 1H), 2.31(m, 1H), 1.81(m, 2H), propylpyrimidin-2-amine 1.06(t, 3H) dihydrochloride 352 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.18(d, 1H), 7.92-7.85(dd, aminopyrrolidin-1-yl)-6- 1H), 7.52(m, 1H), 6.35(s, 1H), 6.78-4.18(m, 5H), 2.68(m, propylpyrimidin-2-yl]-3- 2H), 2.58(m, 1H), 2.35(m, 1H), 1.82(m, 2H), 1.05(t, 3H) (trifluoromethyl)benzene- 1,4-diamine dihydrochloride 353 (S)-5-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.07(d, 1H), 7.87(m, 1H), 1-yl)-6-propylpyrimidin-2- 7.43(t, 1H), 6.33(s, 1H), 4.14-3.84(m, 5H), 2.69(m, 2H), ylamino]-2- 2.56(m, 1H), 2.23(m, 1H), 1.80(m, 2H), 1.06(t, 3H) fluorobenzonitrile dihydrochloride 354 (S)-5-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.02(d, H), 7.68(d, 1H), 1-yl)-6-propylpyrimidin-2- 7.45(d, 1H), 6.31(s, 1H), 4.08-3.82(m, 5H), 2.68(m, 2H), ylamino]-2- 2.58(m, 1H), 2.52(s, 3H), 2.28(m, 1H), 1.80(m, 2H), methylbenzonitrile 1.06(t, 3H) dihydrochloride 355 (S)-2-amino-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.64(d, 1H), 7.45(m, 1H), aminopyrrolidin-1-yl)-6- 6.94(m, 1H), 6.25(s, 1H), 4.13-3.70(m, 5H), 2.65(m, 2H), propylpyrimidin-2- 2.55(m, 1H), 2.28(m, 1H), 1.78(m, 2H), 1.05(t, 3H) ylamino]benzonitrile dihydrochloride

TABLE 1-37 Example Compound NMR Spectrum 356 (S)-benzyl 5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.34(d, 1H), 7.44-7.31(m, aminopyrrolidin-1-yl)-6- 5H), 7.09-7.00(dd, 2H), 6.21(d, 1H), 5.20(d, 2H), 4.01- propylpyrimidin-2-ylamino]- 3.72(m, 5H), 3.80(s, 3H), 2.64(m, 2H), 2.62(m, 1H), 2-methoxyphenylcarbamate 2.54-2.29(m, 1H), 1.78(m, 2H), 1.04(t, 3H) dihydrochloride 357 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.12(d, 1H), 7.85(m, 1H), yl)-N-[4-fluoro-3- 7.41(m, 1H), 6.30(s, 1H), 4.09-3.88(m, 5H), 2.71(m, 2H), (trifluoromethyl)phenyl]-6- 2.64(m, 1H), 2.30(m, 1H), 1.82(m, 2H), 1.07(m, 3H) propylpyrimidin-2-amine dihydrochloride 358 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.81-8.68(m, 1H), 7.83(m, yl)-N-(4-fluoro-3- 1H), 7.49(m, 1H), 6.36(s, 1H), 4.18-3.76(m, 5H), 2.70(m, nitrophenyl)-6- 2H), 2.58(m, 1H), 2.32(m, 1H), 1.82(m, 2H), 1.06(t, 3H) propylpyrimidin-2-amine dihydrochloride 359 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.54(m, 1H), 7.43(m, 1H), aminopyrrolidin-1-yl)-6- 7.02(m, 1H), 6.25(d, 1H), 4.15-3.71(m, 5H), 2.66(m, 2H), propylpyrimidin-2-yl]-3- 2.57(m, 1H), 2.30(m, 1H), 1.79(m, 2H), 1.05(t, 3H) nitrobenzene-1,4-diamine dihydrochloride 360 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.34-8.30(d, 2H), 7.78(s, yl)-N-[3,5- 1H), 6.40(s, 1H), 4.16-3.77(m, 5H), 2.73(t, 2H), 2.54(m, bis(trifluoromethyl)phenyl]- 1H), 2.26(m, 1H), 1.82(m, 2H), 0.90(t, 3H) 6-propylpyrimidin-2-amine dihydrochloride 361 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 6.81-6.78(m, 2H), 6.35(s, yl)-N-(3,5- 1H), 6.28(s, 1H), 4.15-3.99(m, 4H), 3.85(s, 6H), 3.84- dimethoxyphenyl)-6- 3.79(m, 1H), 2.66(t, 2H), 2.59(m, 1H), 2.50(m, 1H), propylpyrimidin-2-amine 1.81(m, 2H), 1.05(t, 3H) dihydrochloride 362 (S)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 6.53(s, 1H), 6.26(m, 2H), aminopyrrolidin-1-yl)-6- 5.83(s, 1H), 3.82(br, 1H), 3.65(m, 2H), 3.48(br, 1H), propylpyrimidin-2- 3.30(br, 1H), 2.46(m, 2H), 2.21(m, 1H), 1.89(m, 1H), yl]amino}benzonitrile 1.71(m, 2H), 0.97(t, 3H) 363 (S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.76(s, 1H), 7.62(m, 1H), 1-yl)-6-propylpyrimidin-2- 7.41(m, 2H), 5.86(s, 1H), 3.88-3.77(br, 1H), 3.65(m, 2H), ylamino]benzenesulfonamide 3.53(br, 2H), 2.48(m, 2H), 2.21(m, 1H), 1.87(m, 1H), 1.74(m, 2H), 0.98(t, 3H) 364 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.73(br, 1H), 7.04(t, 1H), (methoxymethyl)pyrrolidin- 6.97(br, 1H), 6.63(br, 1H), 6.30(m, 1H), 5.68(br, 1H), 1-yl]-6-propylpyrimidin-2- 4.63(br, 1H), 3.92(m, 3H), 3.45(br, 1H), 3.39(s, 3H), yl}benzene-1,3-diamine 3.18(br, 1H), 3.14(m, 1H), 2.45(t, 2H), 2.10-1.96(m, 4H), 1.68(m, 3H), 0.99(t, 3H) 365 (S)-4-fluoro-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.82(br, 1H), 6.97(br, 1H), (methoxymethyl)pyrrolidin- 6.85(m, 1H), 6.51(br, 1H), 5.68(s, 1H), 4.46(br, 1H), 1-yl]-6-propylpyrimidin-2- 3.89(br, 2H), 3.45(br, 1H), 3.39(s, 3H), 3.34(m, 1H), yl}benzene-1,3-diamine 3.12(m, 1H), 2.45(t, 2H), 2.09-1.98(m, 4H), 1.68(m, 3H), 0.97(t, 3H)

TABLE 1-38 Example Compound NMR Spectrum 366 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl3) δ 7.72(br, 1H), 6.90(m, 2H), (methoxymethyl)pyrrolidin- 6.57(br, 1H), 5.67(s, 1H), 4.51(br, 1H), 3.93-3.78(br, 2H), 1-yl]-6-propylpyrimidin-2-yl}- 3.45(br, 1H), 3.40(s, 3H), 3.22(m, 1H), 3.13(m, 1H), 4-methylbenzene-1,3- 2.45(m, 2H), 2.11(s, 3H), 1.99(m, 4H), 1.69(m, 3H), diamine 0.98(t, 3H) 367 (S)-4-methoxy-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.62(br, 1H), 7.00(br, 1H), (methoxymethyl)pyrrolidin- 6.70(m, 2H), 5.66(s, 1H), 4.72(br, 1H), 3.92(br, 2H), 1-yl]-6-propylpyrimidin-2- 3.81(s, 3H), 3.40(m, 1H), 3.39(s, 3H), 3.29(m, 1H), yl}benzene-1,3-diamine 3.17(m, 1H), 2.44(t, 2H), 2.02(m, 4H), 1.71(m, 2H), 0.97(t, 3H) 368 (S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.40(br, 1H), 6.99(m, 1H), (methoxymethyl)pyrrolidin- 6.78(m, 1H), 6.68(s, 1H), 4.40(br, 1H), 3.75(br, 1H), 1-yl]-6-propylpyrimidin-2- 3.59(t, 2H), 3.53(br, 1H), 3.38(s, 3H), 3.36(m, 1H), yl}indolin-6-amine 3.26(t, 1H), 2.99(t, 2H), 2.46(t, 2H), 2.09-1.95(m, 4H), 1.72(m, 2H), 0.96(t, 3H) 369 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 7.17(s, 1H), 6.94(s, 1H), aminopyrrolidin-1-yl)-6- 6.81(br, 1H), 5.65(s, 1H), 3.71(m, 2H), 3.56(br, 1H), propylpyrimidin-2-yl]-4- 2.45(m, 2H), 2.19(m, 1H), 2.12(s, 3H), 1.81(m, 1H), methylbenzene-1,3-diamine 1.70(m, 2H), 1.26(br, 2H), 0.97(t, 3H) 370 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.90(m, 1H), 7.65(m, 1H), aminopyrrolidin-1-yl)-6- 7.41(t, 1H), 6.32(s, 1H), 4.16-3.77(m, 5H), 2.69(m, 2H), propylpyrimidin-2-yl]-4- 2.57(m, 1H), 2.51(m, 1H), 1.81(m, 2H), 1.00(t, 3H) fluorobenzene-1,3-diamine dihydrochloride 371 (S)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.85(d, 1H), 7.78(s, 1H), aminopyrrolidin-1-yl)-6- 7.28(m, 1H), 6.36(s, 1H), 4.17-3.76(m, 5H), 2.70(m, 2H), propylpyrimidin-2- 2.60(m, 1H), 2.33(m, 1H), 1.82(m, 2H), 1.06(t, 3H) yl]amino}benzonitrile dihydrochloride 372 (S)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.05(brs, 1H), 7.37(d, 1H), nitrophenyl)-4-[3- 7.30(br, 1H), 7.15(br, 1H), 5.75(s, 1H), 3.86-3.30(m, 5H), (cyclopropylmethylamino)pyrrol- 2.55(d, 2H), 2.47(t, 2H), 2.23(m, 1H), 1.90(br, 1H), idin-1-yl]-6-propylpyrimidin-2-amine 1.72(m, 3H), 1.00(t, 4H), 0.55(d, 2H), 0.15(m, 2H) 373 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.16(brs, 1H), 7.40(br, 1H), (cyclopropylmethylamino)pyrrolidin- 7.17(br, 1H), 7.12(t, 2H), 5.74(s, 1H), 3.90-3.15(m, 5H), 1-yl]-N-(4-fluoro-3- 2.56(d, 2H), 2.47(t, 2H), 2.23(m, 1H), 1.90(br, 1H), nitrophenyl)-6- 1.74(m, 3H), 0.97(t, 4H), 0.51(d, 2H), 0.16(d, 2H) propylpyrimidin-2-amine 374 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.06(brs, 1H), 7.30(m, 1H), (cyclopropylmethylamino)pyrrol- 7.17(d, 1H), 7.10(br, 1H), 5.72(s, 1H), 3.91-3.40(m, 5H), idin-1-yl]-N-(4-methyl-3- 2.57(m, 2H), 2.54(s, 3H), 2.47(t, 2H), 2.23(m, 1H), nitrophenyl)-6- 1.90(br, 1H), 1.75(m, 3H), 0.98(t, 3H), 0.52(d, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 375 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.26(brs, 1H), 7.77(d, 1H), (cyclopropylmethylamino)pyrrol- 7.44(m, 1H), 7.37(m, 1H), 5.74(s, 1H), 3.92-3.60(m, 5H), idin-1-yl]-N-(3- 2.64(m, 2H), 2.48(t, 2H), 2.29(m, 1H), 2.02(m, 1H), nitrophenyl)-6- 1.72(m, 2H), 1.00(m, 4H), 0.56(m, 4H), 0.22(m, 2H) propylpyrimidin-2-amine

TABLE 1-39 Example Compound NMR Spectrum 376 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(m, 1H), 7.56(m, 1H), (cyclopropylmethylamino)pyrrol- 7.09(m, 2H), 5.73(s, 1H), 3.84-3.16(m, 5H), 2.60(m, 2H), idin-1-yl]-6- 2.47(t, 2H), 2.22(m, 1H), 1.88(br, 1H), 1.70(m, 3H), propylpyrimidin-2-ylamino}- 0.99(m, 4H), 0.50(m, 2H), 0.15(m, 2H) 2-fluorobenzonitrile 377 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(d, 1H), 7.46(d, 1H), (cyclopropylmethylamino)pyrrol- 7.18(d, 1H), 7.02(br, 1H), 5.71(s, 1H), 3.80-3.00(m, 5H), idin-1-yl]-6- 2.54(d, 2H), 2.48-2.45(m, 5H), 2.21(m, 1H), 1.88(br, 1H), propylpyrimidin-2-ylamino}- 1.74(m, 3H), 0.98(t, 4H), 0.54(m, 2H), 0.17(m, 2H) 2-methylbenzonitrile 378 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.86(s, 1H), 7.28(d, 1H), (cyclopropylmethylamino)pyrrol- 7.17(t, 1H), 6.96(br, 1H), 6.84(d, 1H), 5.69(s, 1H), 4.00- idin-1-yl]-N-[3- 3.20(m, 5H), 2.54(d, 2H), 2.49(s, 3H), 2.44(m, 2H), (methylthio)phenyl]-6- 2.20(m, 1H), 1.86(br, 1H), 1.73(m, 3H), 0.97(m, 4H), propylpyrimidin-2-amine 0.50(m, 2H), 0.15(m, 2H) 379 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.54(s, 1H), 7.40(m, 1H), (cyclopropylmethylamino)pyrrol- 7.33(m, 1H), 7.18(m, 2H), 5.71(s, 1H), 4.10-3.00(m, 5H), idin-1-yl]-6-propyl-N-[3- 2.53(m, 2H), 2.46(t, 2H), 2.21(m, 1H), 1.88(br, 1H), (trifluoromethyl)phenyl]pyrim- 1.72(m, 3H), 0.97(t, 4H), 0.50(m, 2H), 0.15(m, 2H) idin-2-amine 380 (S)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.64(s, 1H), 7.03(d, 1H), methylphenyl)-4-[3- 6.86(d, 1H), 6.70(brs, 1H), 5.71(s, 1H), 3.84-3.15(m, (cyclopropylmethylamino)pyrrol- 5H), 2.55(m, 2H), 2.47(t, 2H), 2.27(s, 3H), 2.23(m, 1H), idin-1-yl]-6- 1.87(br, 1H), 1.71(m, 3H), 0.98(m, 4H), 0.50(m, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 381 (S)-N-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.03(s, 1H), 7.27(br, 1H), methylphenyl)-4-[3- 7.18(m, 1H), 7.09(m, 1H), 5.68(s, 1H), 4.00-3.15(m, 5H), (cyclopropylmethylamino)pyrrol- 2.55(m, 2H), 2.47(m, 2H), 2.31(s, 3H), 2.23(m, 1H), idin-1-yl]-6- 1.91(br, 1H), 1.68(m, 3H), 0.98(m, 4H), 0.52(m, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 382 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.48(brs, 1H), 7.39(brs, 1H), (cyclopropylmethylamino)pyrrol- 7.06(m, 2H), 5.71(s, 1H), 4.00-3.00(m, 5H), 2.53(m, 2H), idin-1-yl]-N-[4-fluoro-3- 2.46(m, 2H), 2.21(m, 1H), 1.88(m, 1H), 1.72(m, 3H), (trifluoromethyl)phenyl]-6- 0.97(m, 4H), 0.52(m, 2H), 0.14(m, 2H) propylpyrimidin-2-amine 383 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.16(s, 1H), 6.96(m, 2H), (cyclopropylmethylamino)pyrrol- 5.64(s, 1H), 3.71-3.31(m, 7H), 2.54(dd, 2H), 2.46(m, idin-1-yl]-6- 2H), 2.19(m, 1H), 2.12(s, 3H), 1.87(br, 1H), 1.71(m, 3H), propylpyrimidin-2-yl}-4- 0.98(t, 4H), 0.51(m, 2H), 0.14(m, 2H) methylbenzene-1,3-diamine 384 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.17(s, 1H), 7.09-6.99(m, (cyclopropylmethylamino)pyrrol- 2H), 6.32(d, 1H), 5.66(s, 1H), 3.59-3.41(m, 7H), 2.53(m, idin-1-yl]-6- 2H), 2.32(m, 2H), 2.20(m, 1H), 1.87(br, 1H), 1.68(m, propylpyrimidin-2- 3H), 0.96(m, 4H), 0.51(m, 2H), 0.14(m, 2H) yl}benzene-1,3-diamine 385 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.16(br, 1H), 7.85(br, 1H), (cyclopropylmethylamino)pyrrol- 7.42(t, 1H), 6.31(s, 1H), 4.12-3.74(m, 5H), 3.05(m, 2H), idin-1-yl]-6- 2.69(t, 2H), 2.58(br, 1H), 2.35(br, 1H), 1.80(m, 2H), propylpyrimidin-2-ylamino}- 1.14(m, 1H), 1.05(t, 3H), 0.75(m, 2H), 0.48(m, 2H) 2-fluorobenzonitrile dihydrochloride

TABLE 1-40 Example Compound NMR Spectrum 386 (S)-4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.77(d, 1H), 7.60(m, 1H), (cyclopropylmethylamino)pyrrol- 7.46(d, 1H), 6.33(s, 1H), 4.24-3.93(m, 5H), 3.05(m, 2H), idin-1-yl]-N-(4-methyl-3- 2.70(t, 2H), 2.63(m, 1H), 2.57(s, 3H), 2.37(br, 1H), nitrophenyl)-6- 1.79(m, 2H), 1.22(m, 1H), 1.18(t, 3H), 0.76(m, 2H), propylpyrimidin-2-amine 0.46(m, 2H) dihydrochloride 387 3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(d, 1H), 7.85-7.78(m, (cyclopropylmethylamino)pyrrol- 1H), 7.59(m, 2H), 6.35(s, 1H), 4.19-3.73(m, 5H), 3.07- idin-1-yl]-6- 3.00(m, 2H), 2.67(t, 2H), 2.63-2.60(m, 2H), 1.79(m, 2H), propylpyrimidin-2- 1.22(m, 1H), 1.16(t, 3H), 0.74(m, 2H), 0.48(m, 2H) ylamino}benzonitrile dihydrochloride 388 (S)-{1-[6-ethyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.45(t, 2H), 7.18(t, 2H), fluorophenylamino)pyrimidin- 6.28-6.11(m, 1H), 4.35-4.09(d, 1H), 3.70-3.45(m, 4H), 4-yl]pyrrolidin-2- 2.60(q, 2H), 2.10(m, 4H), 1.27(t, 3H) yl}methanol 389 (S)-N-{1-[6-ethyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.42(m, 2H), 7.19(t, 2H), fluorophenylamino)pyrimidin- 6.14-6.10(m, 1H), 4.50(m, 1H), 3.86-3.40(m, 4H), 4-yl]pyrrolidin-3- 2.60(m, 2H), 2.31(m, 1H), 2.10(m, 1H), 1.95(s, 3H), yl}acetamide 1.27(t, 3H) 390 (S)-4-ethyl-N-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.43(m, 2H), 7.19(t, 2H), fluorophenyl)-6-(2- 6.28-6.11(m, 1H), 4.44-4.21(d, 1H), 3.59-3.54(m, 4H), methoxymethylpyrrolidin-1- 3.24(d, 3H), 2.61(q, 2H), 2.04(m, 4H), 1.26(t, 3H) yl)pyrimidin-2-amine 391 4-ethyl-N-(4-fluorophenyl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.43(t, 2H), 7.16(t, 2H), 6-(2-methylpyrrolidin-1- 6.13-6.07(m, 1H), 4.37-4.18(d, 1H), 3.69-3.44(m, 2H), yl)pyrimidin-2-amine 3.35(s, 3H), 2.63(q, 2H), 2.14(m, 3H), 1.82(m, 1H), 1.27(t, 3H) 392 (S)-4-ethyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.45(m, 2H), 7.19(m, 2H), (ethylamino)pyrrolidin-1-yl]- 6.14(s, 1H), 3.87-3.58(m, 5H), 2.84(m, 2H), 2.63(m, 2H), N-(4-fluorophenyl)pyrimidin- 2.36(m, 1H), 2.06(m, 1H), 1.27-1.22(m, 6H) 2-amine 393 (S)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.58(m, 1H), phenoxypyrrolidin-1-yl)-6- 7.38(brs, 1H), 7.20(m, 3H), 7.20(d, 1H), 7.00(t, 1H), propylpyrimidin-2- 6.90(m, 2H), 5.77(s, 1H), 5.08(s, 1H), 3.77(m, 4H), ylamino]benzonitrile 2.51(t, 2H), 2.40(m, 1H), 2.27(m, 1H), 1.73(q, 2H), 0.98(t, 3H) 394 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.80(s, 1H), 8.77(t, 1H), cyanophenylamino)-6- 8.58(d, 1H), 8.17(d, 1H), 8.07(m, 1H), 7.82-7.75(m, 1H), propylpyrimidin-4- 7.59-7.51(m, 2H), 6.32(d, 1H), 4.58-4.50(m, 1H), 3.99(m, yl]pyrrolidin-3-yl}-2-(pyridin- 1H), 3.82(m, 3H), 3.78-3.56(m, 3H), 2.66(m, 2H), 3-yl)acetamide 2.39(m, 1H), 2.14(m, 1H), 1.80(m, 2H), 1.06(t, 3H) dihydrochloride

TABLE 1-41 Example Compound NMR Spectrum 395 (S)-2-amino-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.33(s, 1H), 7.61(m, 2H), cyanophenylamino)-6- 7.34(t, 1H), 7.20(d, 1H), 5.75(s, 1H), 4.63(m, 1H), propylpyrimidin-4- 3.81(m, 3H), 3.38(s, 4H), 2.51(t, 2H), 2.33(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.05(m, 1H), 1.71(m, 2H), 0.98(t, 3H) 396 (S)-3-(4-{3-[4- ¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.77(d, 1H), (dimethylamino)benzylami- 7.45(t, 1H), 7.34(m, 3H), 6.81(d, 2H), 6.06(s, 1H), no]pyrrolidin-1-yl}-6- 4.21(s, 2H), 4.04(m, 2H), 3.81-3.64(m, 3H), 2.96(s, 6H), propylpyrimidin-2- 2.56(t, 3H), 2.31(m, 1H), 1.77(q, 2H), 1.00(t, 3H) ylamino)benzonitrile dihydrochloride 397 (S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CD₃OD) δ 8.08-8.01(d, 1H), 7.86(m, (hydroxymethyl)pyrrolidin-1- 1H), 7.41(m, 1H), 6.41-6.23(d, 1H), 4.34-4.18(d, 1H), yl]-6-propylpyrimidin-2- 3.71-3.55(m, 4H), 2.63(t, 2H), 2.11(m, 4H), 1.77(m, 2H), ylamino}benzonitrile 1.05(t, 3H) hydrochloride 398 (S)-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.58-8.38(d, 1H), 7.41(m, nitrophenylamino)-6- 1H), 7.03(m, 1H), 6.34-7.17(d, 1H), 4.40-4.17(d, 1H), propylpyrimidin-4- 3.88-3.62(m, 4H), 2.61(t, 2H), 2.25-2.01(m, 4H), 1.76(m, yl]pyrrolidin-2-yl}methanol 2H), 1.04(t, 3H) hydrochloride 399 (S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.32(s, 1H), 6.92(d, 1H), methylphenylamino)-6- 6.78(brs, NH), 6.67(d, 1H), 5.69(s, 1H), 4.41(brs, 1H), propylpyrimidin-4- 3.80(m, 1H), 3.70(brs, 1H), 3.59(m, 1H), 3.46(m, 1H), yl]pyrrolidin-2-yl}methanol 3.30(m, 1H), 2.44(t, 2H), 2.11(s, 3H), 2.02(m, 3H), 1.85(m, 1H), 1.71(m, 2H), 0.98(t, 3H) 400 (S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.43(d, 1H), 6.86(m, 2H), fluorophenylamino)-6- 6.63(brs, 1H), 5.70(s, 1H), 4.38(s, 1H), 3.86(s, 1H), propylpyrimidin-4- 3.76(m, 1H), 3.58(m, 1H), 3.45(m, 1H), 3.29(brs, 1H), yl]pyrrolidin-2-yl}methanol 2.45(t, 3H), 2.01(m, 3H), 1.85(m, 1H), 1.70(m, 2H), 0.97(t, 3H) 401 (S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.52(s, 1H), 7.00(d, 1H), chlorophenylamino)-6- 6.68(m, 1H), 5.73(s, 1H), 4.43(m, 1H), 4.22(m, 1H), propylpyrimidin-4- 3.82(m, 1H), 3.62(m, 1H), 3.49(m, 1H), 3.34(m, 1H), yl]pyrrolidin-2-yl}methanol 2.49(t, 2H), 2.05(m, 2H), 1.63(m, 4H), 0.98(t, 3H) 402 (S)-3-[4-(2-formylpyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 9.61(s, 1H), 8.12(s, 1H), 1-yl)-6-propylpyrimidin-2- 7.57(d, 1H), 7.34(t, 1H), 7.24(t, 1H), 7.13(s, 1H), 5.84(s, ylamino]benzonitrile 1H), 4.54(s, 1H), 3.62-3.52(m, 2H), 2.53(t, 2H), 2.22(s, 1H), 2.09(m, 3H), 1.73(m, 2H), 0.99(t, 3H) 403 (S)-3-(4-{2- ¹H-NMR(400 MHz, CD₃OD) δ 8.32(s, 1H), 7.83(d, 1H), [(methylamino)methyl]pyrrol- 7.41(t, 1H), 7.22(d, 1H), 5.94(s, 1H), 4.30(brs, 1H), 3.56- idin-1-yl}-6-propylpyrimidin- 3.38(m, 2H), 2.86(s, 1H), 2.62(m, 1H), 2.48(t, 2H), 2-ylamino)benzonitrile 2.40(s, 3H), 2.04(m, 4H), 1.74(m, 2H), 0.99(t, 3H)

TABLE 1-42 Example Compound NMR Spectrum 404 (S)-3-(4-{2- ¹H-NMR(400 MHz, CDCl₃) δ 8.75(s, 1H), 8.45(s, 1H), [(cyclobutylamino)methyl]pyrrol- 7.87(s, 1H), 7.31(m, 1H), 7.19(d, 1H), 5.80(s, 1H), idin-1-yl}-6- 4.52(s, 1H), 3.45-3.31(m, 2H), 2.92-2.81(m, 2H), 2.53(m, propylpyrimidin-2- 2H), 2.23-2.01(m, 7H), 1.75(m, 4H), 0.88(t, 3H) ylamino)benzonitrile 405 (S)-3-(4-{2-[(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(s, 1H), 7.64(s, 1H), fluorobenzylamino)methyl]pyrrol- 7.33-7.19(m, 4H), 6.94(m, 2H), 5.75(s, 1H), 4.44(s, 1H), idin-1-yl}-6- 3.85(s, 2H), 3.45-3.31(m, 2H), 2.87-2.76(m, 2H), 2.48(m, propylpyrimidin-2- 2H), 2.02(m, 4H), 1.71(m, 2H), 0.98(t, 3H) ylamino)benzonitrile 406 (S)-3-(4-propyl-6-{2- ¹H-NMR(400 MHz, CDCl₃) δ 9.44(s, 1H), 8.56(s, 1H), [(propylamino)methyl]pyrrol- 7.99(m, 1H), 7.30(m, 1H), 7.18(d, 1H), 5.80(s, 1H), idin-1-yl}pyrimidin-2- 4.69(s, 1H), 3.48-3.32(m, 3H), 3.02(m, 1H), 2.82(m, 2H), ylamino)benzonitrile 2.54(t, 2H), 2.16(m, 1H), 1.98(m, 2H), 1.88-1.75(m, 5H), 0.98(t, 3H), 0.89(t, 3H) 407 (S)-3-(4-{2-[(2- ¹H-NMR(400 MHz, CDCl₃) δ 9.11(s, 1H), 8.48(s, 1H), hydroxyethylamino)methyl]pyrrol- 7.89(d, 1H), 7.31(m, 1H), 7.17(d, 1H), 5.78(s, 1H), idin-1-yl}-6- 4.30(m, 1H), 4.10(m, 1H), 3.92(m, 1H), 3.45(m, 1H), propylpyrimidin-2- 3.37(m, 2H), 3.14-3.04(m, 2H), 2.92(m, 1H), 2.55(t, 2H), ylamino)benzonitrile 2.23(m, 1H), 1.97(m, 2H), 1.80-1.75(m, 3H), 1.01(t, 3H) 408 N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.14-8.02(d, 1H), 7.85(m, cyanophenylamino)-6- 1H), 7.58-7.52(m, 2H), 6.29(d, 1H), 4.52(m, 1H), 3.95- propylpyrimidin-4- 3.48(m, 4H), 2.66(m, 2H), 2.33(m, 1H), 2.10(m, 1H), yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H), 1.77(m, 2H), 1.05(m, 3H) hydrochloride 409 N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.97(d, 1H), 8.03(m, 1H), nitrophenylamino)-6- 7.79(m, 1H), 7.60(m, 1H), 6.27(m, 1H), 4.53(m, 1H), propylpyrimidin-4- 3.99-3.48(m, 4H), 2.66(m, 2H), 2.33(m, 1H), 2.10(m, yl]pyrrolidin-3-yl}acetamide 1H), 1.96(s, 3H), 1.78(m, 2H), 1.06(m, 3H) hydrochloride 410 N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.64-8.52(d, 1H), 7.71- nitrophenylamino)-6- 7.66(m, 2H), 6.32(d, 1H), 4.52(m, 1H), 4.10-3.62(m, 4H), propylpyrimidin-4- 2.69(m, 2H), 2.34(m, 1H), 2.13(m, 1H), 1.99(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.77(m, 2H), 1.04(m, 3H) hydrochloride 411 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.56(s, 1H), 7.41(m, 1H), methylpyrrolidin-1-yl)-6- 6.99(d, 1H), 6.21(m, 1H), 4.52-4.23(m, 2H), 3.81-3.48(m, propylpyrimidin-2-yl]-3- 2H), 2.63(t, 2H), 2.15(m, 3H), 1.74(m, 2H), 1.25(m, 3H), nitrobenzene-1,4-diamine 1.03(t, 3H) hydrochloride 412 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.15-8.10(m, 1H), 7.66- methylpyrrolidin-1-yl)-6- 7.65(m, 1H), 7.30-7.25(m, 1H), 6.29-6.17(d, 1H), 4.45- propylpyrimidin-2-yl]-3- 4.24(m, 1H), 3.78-3.47(m, 2H), 2.63(m, 2H), 2.21- (trifluoromethyl)benzene- 2.07(m, 3H), 1.78(m, 3H), 1.27(m, 3H), 1.05(t, 3H) 1,4-diamine hydrochloride 413 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.12-8.03(d, 1H), 7.65(m, (cyclopropylmethylamino)pyrrol- 1H), 7.44(d, 1H), 6.32(s, 1H), 4.14(m, 2H), 3.94-3.75(m, idin-1-yl]-6- 3H), 3.06-3.00(m, 2H), 2.68(t, 2H), 2.61(m, 1H), 2.52(s, propylpyrimidin-2-ylamino}- 3H), 2.38-2.36(m, 1H), 1.82-1.76(m, 2H), 1.15(m, 1H), 2-methylbenzonitrile 1.05(t, 3H), 0.74(m, 2H), 0.48(m, 2H) dihydrochloride

TABLE 1-43 Example Compound NMR Spectrum 414 (S)-2-methyl-5-{4-propyl-6- ¹H-NMR(400 MHz, CD₃OD) δ 8.37(d, 1H), 7.64(d, 1H), [3-(propylamino)pyrrolidin- 7.26(d, 1H), 5.87(d, 1H), 4.00-3.30(m, 5H), 2.90-2.60(m, 1-yl]pyrimidin-2- 2H), 2.48(t, 2H), 2.44(s, 3H), 2.40-2.25(m, 1H), 2.05- ylamino}benzonitrile 1.90(m, 1H), 1.80-1.50(m, 4H), 1.00-0.90(m, 6H) 415 (S)-2-methyl-5-(4-{3-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.66(d, 1H), (methylthio)propylamino]pyrrol- 7.26(d, 1H), 5.87(s, 1H), 3.90-3.30(m, 5H), 2.81(t, 2H), idin-1-yl}-6- 2.57(t, 2H), 2.48(t, 2H), 2.45(s, 3H), 2.30-2.20(m, 1H), propylpyrimidin-2- 2.09(s, 3H), 2.00-1.90(m, 1H), 1.84(t, 2H), 1.75(q, 2H), ylamino)benzonitrile 0.98(t, 3H) 416 (S)-5-(4-{3-[(1H-pyrrol-2- ¹H-NMR(400 MHz, CD₃OD) δ 8.35(s, 1H), 7.66(dd, 1H), yl)methylamino]pyrrolidin-1- 7.26(d, 1H), 6.69(s, 1H), 6.10-6.00(m, 2H), 5.84(s, 1H), yl}-6-propylpyrimidin-2- 3.86(s, 2H), 3.80-3.30(m, 5H), 2.47(t, 2H), 2.45(s, 3H), ylamino)-2- 2.25-2.15(m, 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, methylbenzonitrile 3H) 417 (S)-5-{4-[3-(4- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.65(d, 1H), hydroxybenzylamino)pyrrol- 7.30-7.20(m, 3H), 6.77(d, 1H), 5.85(s, 1H), 3.82(s, 2H), idin-1-yl]-6-propylpyrimidin- 3.80-3.30(m, 5H), 2.48(t, 2H), 2.44(s, 3H), 2.30-2.20(m, 2-ylamino}-2- 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) methylbenzonitrile 418 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.35(s, 1H), 7.66(d, 1H), (isopropylamino)pyrrolidin- 7.25(d, 1H), 5.86(s, 1H), 4.00-3.35(m, 5H), 3.01(t, 1H), 1-yl]-6-propylpyrimidin-2- 2.47(t, 2H), 2.44(s, 3H), 2.35-2.25(m, 1H), 1.90-1.85(m, ylamino}-2- 1H), 1.73(q, 2H), 1.20-1.10(m, 6H), 0.98(t, 3H) methylbenzonitrile 419 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.33(s, 1H), 7.67(d, 1H), (cyclobutylamino)pyrrolidin- 7.25(d, 1H), 5.84(s, 1H), 3.90-3.30(m, 6H), 2.47(t, 2H), 1-yl]-6-propylpyrimidin-2- 2.44(s, 3H), 2.30-2.15(m, 3H), 2.00-1.60(m, 7H), 0.98(t, ylamino}-2- 3H) methylbenzonitrile 420 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.64(d, 1H), (cyclopentylamino)pyrrolidin- 7.25(d, 1H), 5.85(s, 1H), 4.00-3.35(m, 5H), 3.21(t, 1H), 1-yl]-6-propylpyrimidin-2- 2.47(t, 2H), 2.44(s, 3H), 2.35-2.25(m, 1H), 2.05-1.80(m, ylamino}-2- 3H), 1.80-1.50(m, 6H), 1.40-1.30(m, 2H), 0.99(t, 3H) methylbenzonitrile 421 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.35(s, 1H), 7.63(d, 1H), (cyclohexylamino)pyrrolidin- 7.23(d, 1H), 5.83(s, 1H), 4.00-3.10(m, 5H), 2.60(t, 1H), 1-yl]-6-propylpyrimidin-2- 2.46(t, 2H), 2.43(s, 3H), 2.30-2.20(m, 1H), 2.00-1.60(m, ylamino}-2- 7H), 1.45-1.05(m, 6H), 0.98(t, 3H) methylbenzonitrile 422 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.00(m, 1H), 7.70- (pentylamino)pyrrolidin-1- 7.61(m, 1H), 7.45(d, 1H), 6.32(s, 1H), 4.20-3.60(m, 5H), yl]-6-propylpyrimidin-2- 3.20-3.00(m, 2H), 2.68(t, 2H), 2.65-2.55(m, 1H), 2.52(s, ylamino}benzonitrile 3H), 2.40-2.25(m, 1H), 1.90-1.70(m, 4H), 1.50-1.30(m, dihydrochloride 4H), 1.05(t, 3H), 1.00-0.90(m, 3H) 423 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.08(d, 1H), 7.75-7.55(m, (neopentylamino)pyrrolidin- 1H), 7.50-7.40(m, 1H), 6.32(s, 1H), 4.30-3.60(m, 5H), 1-yl]-6-propylpyrimidin-2- 3.10-2.90(m, 2H), 2.80-2.60(m, 3H), 2.52(s, 3H), 2.50- ylamino}benzonitrile 2.30(m, 1H), 1.80(q, 2H), 1.12(s, 9H), 1.05(t, 3H) dihydrochloride

TABLE 1-44 Example Compound NMR Spectrum 424 (S)-5-(4-{3-[(4,5- ¹H-NMR(400 MHz, CD₃OD) δ 8.10-8.00(m, 1H), 7.73(d, dimethylfuran-2- 1H), 7.45(d, 1H), 6.48(s, 1H), 6.31(s, 1H), 4.40-4.20(m, yl)methylamino]pyrrolidin-1- 2H), 4.20-3.60(m, 5H), 2.68(t, 2H), 2.60-2.50(m, 1H), yl}-6-propylpyrimidin-2- 2.52(s, 3H), 2.40-2.30(m, 1H), 2.25-2.15(m, 3H), 1.93(s, ylamino)-2- 3H), 1.80(q, 2H), 1.05(t, 3H) methylbenzonitrile dihydrochloride 425 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.24(brs, 1H), 7.71(d, 1H), methylphenylamino)-6- 7.27(d, 1H), 5.89(s, 1H), 4.47(t, 1H), 3.90-3.30(m, 4H), propylpyrimidin-4- 2.49(t, 2H), 2.44(s, 3H), 2.30-2.15(m, 3H), 2.10-2.00(m, yl]pyrrolidin-3- 1H), 1.73(q, 2H), 1.12(t, 3H), 0.98(t, 3H) yl}propionamide 426 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.97(brs, 1H), 7.72(d, 1H), methylphenylamino)-6- 7.35-7.15(m, 6H), 5.92(s, 1H), 4.50-4.40(m, 1H), 3.90- propylpyrimidin-4- 3.40(m, 6H), 2.50(t, 2H), 2.46(s, 3H), 2.30-2.20(m, 1H), yl]pyrrolidin-3-yl}-2- 2.10-2.00(m, 1H), 1.73(q, 2H), 0.99(t, 3H) phenylacetamide 427 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.28(s, 1H), 7.69(dd, 1H), methylphenylamino)-6- 7.25(d, 1H), 5.88(s, 1H), 4.51(t, 1H), 3.90-3.35(m, 4H), propylpyrimidin-4- 3.09(s, 2H), 2.60-2.45(m, 6H), 2.44(s, 3H), 2.35-2.25(m, yl]pyrrolidin-3-yl}-2- 1H), 2.10-2.00(m, 1H), 1.80-1.65(m, 2H), 1.60-1.50(m, (piperidin-1-yl)acetamide 4H), 1.50-1.40(m, 2H), 0.98(t, 3H) 428 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.84(s, 1H), 8.80-8.70(m, methylphenylamino)-6- 1H), 8.56(d, 1H), 8.10-8.00(m, 2H), 7.70-7.60(m, 1H), propylpyrimidin-4- 7.43(t, 1H), 6.25(d, 1H), 4.55-4.45(m, 1H), 4.10-3.50(m, yl]pyrrolidin-3-yl}-2-(pyridin- 6H), 2.70-2.60(m, 2H), 2.51(d, 3H), 2.40-2.25(m, 1H), 3-yl)acetamide 2.20-2.05(m, 1H), 1.80-1.65(m, 2H), 1.10-1.00(m, 3H) 429 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.50-8.40(m, 2H), 8.29(s, methylphenylamino)-6- 1H), 7.70(dd, 1H), 7.36(d, 2H), 7.26(d, 1H), 5.87(s, 1H), propylpyrimidin-4- 4.48(t, 1H), 3.90-3.30(m, 6H), 2.50-2.40(m, 5H), 2.30- yl]pyrrolidin-3-yl}-2-(pyridin- 2.20(m, 1H), 2.10-2.00(m, 1H), 1.73(q, 2H), 0.98(t, 3H) 4-yl)acetamide 430 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.24(brs, 1H), 7.72(d, 1H), methylphenylamino)-6- 7.30-7.20(m, 2H), 7.00-6.90(m, 2H), 5.86(s, 1H), 4.47(t, propylpyrimidin-4- 1H), 3.90-3.30(m, 6H), 2.48(t, 2H), 2.44(s, 3H), 2.20(m, yl]pyrrolidin-3-yl}-2- 1H), 2.10-2.00(m, 1H), 1.73(q, 2H), 0.98(t, 3H) (thiophen-2-yl)acetamide 431 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.29(s, 1H), 7.70(dd, 1H), methylphenylamino)-6- 5.88(s, 1H), 4.15(t, 1H), 3.90-3.30(m, 4H), 3.02(s, 3H), propylpyrimidin-4- 2.49(t, 2H), 2.44(s, 3H), 2.35-2.25(m, 1H), 2.10-2.00(m, yl]pyrrolidin-3- 1H), 1.73(q, 2H), 0.98(t, 3H) yl}methanesulfonamide 432 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.02(d, 1H), 7.70(d, 1H), methylphenylamino)-6- 7.44(d, 1H), 6.26(s, 1H), 4.30-4.10(m, 1H), 4.00-3.40(m, propylpyrimidin-4- 4H), 3.03(s, 3H), 2.65(t, 2H), 2.52(s, 3H), 2.45-2.30(m, yl]pyrrolidin-3- 1H), 2.20-2.00(m, 1H), 1.77(q, 2H), 1.05(t, 3H) yl}methanesulfonamide hydrochloride

TABLE 1-45 Example Compound NMR Spectrum 433 (S)-1-(1-{2-[(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.00(d, 1H), 7.80-7.60(m, methylphenyl)amino]-6- 1H), 7.44(d, 1H), 6.24(d, 1H), 4.45-4.30(m, 1H), 4.00- propylpyrimidin-4- 3.30(m, 4H), 3.20-3.00(m, 2H), 2.70-2.60(m, 2H), 2.51(s, yl}pyrrolidin-3-yl)-3- 3H), 2.40-2.20(m, 1H), 2.15-2.00(m, 1H), 1.90-1.70(m, ethylurea hydrochloride 2H), 1.20-1.00(m, 6H) 434 (R)-3-(4-{3- ¹H-NMR(400 MHz, CD₃OD) δ 8.40(s, 1H), 7.81(d, 1H), [(diethylamino)methyl]pyrrol- 7.39(t, 1H), 7.22(d, 1H), 5.87(s, 1H), 3.90-3.20(m, 4H), idin-1-yl}-6-propylpyrimidin- 2.80-2.50(m, 6H), 2.48(t, 2H), 2.20-2.10(m, 1H), 1.80- 2-ylamino)benzonitrile 1.65(m, 3H), 1.10(t, 6H), 0.98(t, 3H) 435 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.03(d, 1H), 7.64(brs, 1H), (isopropylamino)pyrrolidin- 7.45(d, 1H), 6.32(s, 1H), 4.20-3.74(m, 5H), 3.56-3.51(m, 1-yl]-6-propylpyrimidin-2- 1H), 2.67(dd, 2H), 2.60(brs, 1H), 2.36-2.31(m, 1H), 1.84- ylamino}-2- 1.74(m, 2H), 1.42(dd, 6H), 1.05(t, 3H) methylbenzonitrile dihydrochloride 436 (S)-N-{1-[6-butyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 8.68-8.56(d, 1H), 7.60(t, methyl-3- 1H), 7.44(d, 1H), 6.24(d, 1H), 4.49(m, 1H), 4.00-3.48(m, nitrophenylamino)pyrimidin- 4H), 2.68(m, 2H), 2.56(s, 3H), 2.33(m, 1H), 2.11(m, 1H), 4-yl]pyrrolidin-3- 1.96(s, 3H), 1.73(m, 2H), 1.45(m, 2H), 0.98(t, 3H) yl}acetamide hydrochloride 437 (S)-N-{1-[6-butyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 8.78-8.66(d, 1H), 7.79(m, fluoro-3- 1H), 7.47(t, 1H), 6.30-6.27(d, 1H), 4.52(m, 1H), 4.48- nitrophenylamino)pyrimidin- 3.48(m, 4H), 2.69(m, 2H), 2.36(m, 1H), 2.10(m, 1H), 4-yl]pyrrolidin-3- 1.95(s, 3H), 1.73(s, 3H), 1.45(m, 2H), 0.98(t, 3H) yl}acetamide hydrochloride 438 (S)-N-{1-[6-butyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 8.65-8.54(d, 1H), 8.40- chloro-3- 8.37(m, 1H), 7.72-7.65(m, 2H), 6.31-6.28(d, 1H), 4.51(m, nitrophenylamino)pyrimidin- 1H), 3.96-3.48(m, 4H), 2.69(m, 2H), 2.32(m, 1H), 4-yl]pyrrolidin-3- 2.13(m, 1H), 1.96(s, 3H), 1.72(m, 2H), 1.45(m, 2H), yl}acetamide hydrochloride 1.00(t, 3H) 439 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 8.06-7.83(m, 2H), 7.36(d, cyanophenylamino)-6- 1H), 6.33(d, 1H), 4.53-4.47(m, 1H), 4.00-3.49(m, 4H), butylpyrimidin-4- 2.70(m, 2H), 2.40(m, 1H), 2.16(m, 1H), 1.97(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.73(m, 2H), 1.44(m, 2H), 1.02(t, 3H) hydrochloride 440 (S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 8.14-8.02(d, 1H), 7.30(d, (trifluoromethyl)phenylamino]- 1H), 6.33(d, 1H), 4.53-4.47(m, 1H), 3.97-3.49(m, 4H), 6-butylpyrimidin-4- 2.71(m, 2H), 2.31(m, 1H), 2.15(m, 1H), 1.96(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.74(m, 2H), 1.47(m, 2H), 0.99(t, 3H) hydrochloride 441 (S)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.74-7.65(d, 1H), 7.34(d, (trifluoromethyl)phenylamino]- 1H), 6.86(d, 1H), 6.13(d, 1H), 4.49(m, 1H), 3.83-3.43(m, 6-butylpyrimidin-4- 4H), 2.63(m, 2H), 2.30(m, 1H), 2.08(m, 1H), 1.94(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.69(m 2H), 1.45(m, 2H), 0.99(t, 3H) hydrochloride 442 (S)-N-(1-{6-butyl-2-[4- ¹H-NMR(400 MHz, CD₃OD) δ 8.19-8.10(d, 1H), 7.76(m, fluoro-3- 1H), 7.38(t, 1H), 6.27(d, 1H), 4.51(m, 1H), 3.89-3.48(m, (trifluoromethyl)phenylami- 4H), 2.68(m, 2H), 2.31(m, 1H), 2.11(m, 1H), 1.95(s, 3H), no]pyrimidin-4-yl}pyrrolidin-3- 1.72(m, 2H), 1.45(m, 2H), 1.00(t, 3H) yl)acetamide hydrochloride

TABLE 1-46 Example Compound NMR Spectrum 443 (S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.09-7.99(d, 1H), 7.87(m, cyano-4- 1H), 7.41(t, 1H), 6.24(d, 1H), 4.51-4.45(m, 1H), 3.89- fluorophenylamino)pyrimidin- 3.48(m, 4H), 2.69(m, 2H), 2.28(m, 1H), 2.11(m, 1H), 4-yl]pyrrolidin-3- 1.95(s, 3H), 1.72(m, 2H), 1.45(m, 2H), 1.00(t, 3H) yl}acetamide hydrochloride 444 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.03(m, 1H), 6.98(t, 1H), fluorophenylamino)-6- 6.74(m, 1H), 6.17(d, 1H), 4.50-4.44(m, 1H), 2.63(m, 2H), butylpyrimidin-4- 2.33(m, 1H), 2.09(m, 1H), 1.95(s, 3H), 1.67(m, 2H), yl]pyrrolidin-3-yl}acetamide 1.43(m, 2H), 0.99(t, 3H) hydrochloride 445 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.18(d, 1H), 7.07(s, 1H), chlorophenylamino)-6- 6.79(m, 1H), 6.16(d, 1H), 4.51-4.45(m, 1H), 3.93-3.47(m, butylpyrimidin-4- 4H), 2.64(m, 2H), 2.34(m, 1H), 2.10(m, 1H), 1.95(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.69(m, 2H), 1.45(m, 2H), 0.99(t, 3H) hydrochloride 446 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.59(d, 1H), 7.40(s, 1H), cyanophenylamino)-6- 6.84(m, 1H), 6.13(m, 1H), 4.49(m, 1H), 3.84-3.44(m, butylpyrimidin-4- 4H), 2.63(m, 2H), 2.32(m, 1H), 2.25(m, 1H), 1.94(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.69(m, 2H), 1.44(m, 2H), 0.99(m, 3H) hydrochloride 447 (S)-2-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.65(s, 1H), 7.42(t, 1H), (methylamino)pyrrolidin-1- 6.94(d, 1H), 6.25(d, 1H), 4.04-3.73(m, 5H), 2.78(d, 3H), yl]pyrimidin-2- 2.59(t, 2H), 2.49(m, 1H), 2.36(m, 1H), 1.71(m, 2H), ylamino}benzonitrile 1.45(m, 2H), 1.00(t, 3H) dihydrochloride 448 (S)-4-butyl-N-(4-methyl-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.81-8.79(m, 1H), 7.56(m, nitrophenyl)-6-[3- 1H), 7.46(m, 1H), 6.33(s, 1H), 4.19-3.81(m, 5H), 2.84(s, (methylamino)pyrrolidin-1- 3H), 2.71(t, 2H), 2.57(s, 3H + 1H), 2.34(m, 1H), 1.75(m, yl]pyrimidin-2-amine 2H), 1.46(m, 2H), 1.01(t, 3H) dihydrochloride 449 (S)-4-butyl-N-(4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.88(m, 1H), 7.72(m,1H), nitrophenyl)-6-[3- 7.48(m, 1H), 6.36(s, 1H), 4.16-3.78(m, 5H), 2.83(s, 3H), (methylamino)pyrrolidin-1- 2.70(m, 2H), 2.59(m, 1H), 2.33(m, 1H), 1.75(m, 2H), yl]pyrimidin-2-amine 1.46(m, 2H), 1.01(m, 3H) dihydrochloride 450 (S)-4-butyl-N-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.73-8.63(m, 1H), 7.68(m, nitrophenyl)-6-[3- 2H), 6.38(s, 1H), 4.19-3.74(m, 5H), 2.84(s, 3H), 2.75(m, (methylamino)pyrrolidin-1- 2H), 2.60(m, 1H), 2.36(m, 1H), 1.73(m, 2H), 1.46(m, yl]pyrimidin-2-amine 2H), 1.01(m, 3H) dihydrochloride 451 (S)-3-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.77-7.74(d, 1H), 7.58(s, (methylamino)pyrrolidin-1- 1H), 7.16(s, 1H), 6.35(s, 1H), 4.09-3.77(m, 5H), 2.83(d, yl]pyrimidin-2- 3H), 2.72(t, 2H), 2.41(m, 1H), 2.36(m, 1H), 1.74(m, 2H), ylamino}benzonitrile 1.02(m, 2H), 0.99(t, 3H) dihydrochloride 452 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.89-7.78(d, 1H), 7.54(m, (methylamino)pyrrolidin-1- 1H), 7.17(m, 1H), 6.36(s, 1H), 4.14-3.79(m, 5H), 2.83(d, yl]pyrimidin-2-yl}-5- 3H), 2.65(t, 2H), 2.54(m, 1H), 2.37(m, 1H), 1.75(m, 2H), (trifluoromethyl)benzene- 1.46(m, 2H), 0.99(t, 3H) 1,3-diamine dihydrochloride

TABLE 1-47 Example Compound NMR Spectrum 453 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.77(d, 1H), 7.47(m, 1H), (methylamino)pyrrolidin-1- 7.02(t, 1H), 6.27(d, 1H), 4.04-3.75(m, 5H), 2.81(d, 3H), yl]pyrimidin-2-yl}-3- 2.58(t, 2H), 2.38(m, 1H), 2.35(m, 1H), 1.70(m, 2H), (trifluoromethyl)benzene- 1.45(m, 2H), 0.98(t, 3H) 1,4-diamine dihydrochloride 454 (S)-4-butyl-N-[4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.13(s, 1H), 7.79(m, 1H), (trifluoromethyl)phenyl]-6- 7.40(t, 1H), 6.33(s, 1H), 5.06-3.79(m, 5H), 2.78(s, 3H), [3-(methylamino)pyrrolidin- 2.69(t, 2H), 2.34(m, 1H), 2.27(m, 1H), 1.74(m, 2H), 1-yl]pyrimidin-2-amine 1.46(m, 2H), 1.00(t, 3H) dihydrochloride 455 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.12(s, 1H), 7.83(m, 1H), (methylamino)pyrrolidin-1- 7.42(t, 1H), 4.04-3.82(m, 5H), 2.81(s, 3H), 2.68(t, 2H), yl]pyrimidin-2-ylamino}-2- 2.35(m, 1H), 2.32(m, 1H), 1.73(m, 2H), 1.46(m, 2H), fluorobenzonitrile 1.00(t, 3H) dihydrochloride 456 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.49(s, 1H), 7.34(m, 2H), (methylamino)pyrrolidin-1- 6.29(d, 1H), 4.11-3.76(m, 5H), 2.82(d, 3H), 2.69(t, 2H), yl]pyrimidin-2-yl}-4- 2.60(m, 1H), 2.38(m, 1H), 1.73(m, 2H), 1.45(m, 2H), fluorobenzene-1,3-diamine 0.98(t, 3H) dihydrochloride 457 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.67(m, 1H), 7.50(m, 1H), (methylamino)pyrrolidin-1- 7.38(m, 1H), 6.33(d, 1H), 4.16-3.77(m, 5H), 2.81(d, 3H), yl]pyrimidin-2-yl}-4- 2.69(t, 2H), 2.52(m, 1H), 2.31(m, 1H), 1.74(m, 2H), chlorobenzene-1,3-diamine 1.48(m, 2H), 1.00(t, 3H) dihydrochloride 458 (S)-2-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.66(d, 1H), 7.40(m, 1H), (ethylamino)pyrrolidin-1- 6.91(d, 1H), 6.24(s, 1H), 4.06-3.70(m, 5H), 3.14(m, 2H), yl]pyrimidin-2- 2.69(m, 2H), 2.59-2.56(m, 1H), 2.36(m, 1H), 1.69(m, ylamino}benzonitrile 2H), 1.48(m, 2H), 1.37(t, 3H), 0.98(t, 3H) dihydrochloride 459 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.19-8.13(m, 1H), 7.80(m, (ethylamino)pyrrolidin-1- 1H), 7.56(m, 2H), 6.35(s, 1H), 4.07-3.77(m, 5H), 3.19(m, yl]pyrimidin-2- 2H), 2.73(t, 2H), 2.60(m, 1H), 2.36(m, 1H), 1.75(m, 2H), ylamino}benzonitrile 1.48(m, 2H), 1.37(m, 3H), 0.99(t, 3H) dihydrochloride 460 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, DMSO-d₆) δ 13.30(brs, 1H), 10.6(brs, (ethylamino)pyrrolidin-1- 1H), 9.53-9.36(m, 2H), 8.09(m, 1H), 7.76(m, 1H), yl]pyrimidin-2-ylamino}-2- 7.48(m, 1H), 6.34(s, 1H), 3.94(m, 7H), 3.04(m, 2H), methylbenzonitrile 2.62(m, 3H), 2.38(m, 2H), 1.70(m, 2H), 1.35(m, 2H), dihydrochloride 0.95(m, 3H), 0.91(m, 3H) 461 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.76-8.60(m, 1H), 7.38(m, (ethylamino)pyrrolidin-1- 1H), 7.02(m, 1H), 6.28(s, 1H), 4.20-3.73(m, 5H), 3.21(m, yl]pyrimidin-2-yl}-3- 2H), 2.62(m, 2H), 2.60(m, 1H), 2.25(m, 1H), 1.47(m, nitrobenzene-1,4-diamine 2H), 1.40(m, 2H), 1.36(m, 3H), 1.00(m, 3H) dihydrochloride 462 (S)-4-butyl-6-[3- ¹H-NMR(400 MHz, DMSO-d₆) δ 13.19(brs, 1H), (ethylamino)pyrrolidin-1-yl]- 10.79(brs, 1H), 9.52-9.38(m, 2H), 8.68(s, 1H), 7.67(s, N-(4-methyl-3- 1H), 7.51(m, 1H), 6.35(s, 1H), 3.99-3.63(m, 5H), 3.05(m, nitrophenyl)pyrimidin-2- 2H), 2.65(m, 2H), 2.39(m, 2H), 1.71(m, 2H), 1.36(m, amine dihydrochloride 2H), 1.27(m, 3H), 0.94(m, 3H)

TABLE 1-48 Example Compound NMR Spectrum 463 (S)-4-butyl-6-[3- ¹H-NMR(400 MHz, DMSO-d₆) δ 13.00(brs, 1H), (ethylamino)pyrrolidin-1-yl]- 10.77(brs, 1H), 9.34(m, 2H), 8.82(s, 1H), 7.83(s, 1H), N-(4-fluoro-3- 7.62(m, 1H), 6.35(s, 1H), 3.93(m, 5H), 3.05(m, 2H), nitrophenyl)pyrimidin-2- 2.65(m, 2H), 2.34(m, 2H), 1.71(m, 2H), 1.37(m, 2H), amine dihydrochloride 1.25(m, 3H), 0.94(m, 3H) 464 (S)-4-butyl-N-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.74-8.64(m, 1H), 7.68(m, nitrophenyl)-6-[3- 2H), 6.38(s, 1H), 4.18-3.77(m, 5H), 3.22(m, 2H), 2.73(m, (ethylamino)pyrrolidin-1- 2H), 2.61(m, 1H), 2.35(m, 1H), 1.75(m, 2H), 1.40(m, yl]pyrimidin-2-amine 2H), 1.39(m, 3H), 1.00(m, 3H) dihydrochloride 465 (S)-3-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.17-7.87(m, 2H), 7.39(s, (ethylamino)pyrrolidin-1- 1H), 6.38(d, 1H), 4.21-3.78(m, 5H), 3.19(m, 2H), 2.75(m, yl]pyrimidin-2- 2H), 2.59(m, 1H), 1.34(m, 1H), 1.76(m, 2H), 1.40(m, ylamino}benzonitrile 2H), 1.39(m, 3H), 1.01(m, 3H) dihydrochloride 466 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.18-8.03(m, 1H), 7.98- (ethylamino)pyrrolidin-1- 7.88(m, 1H), 7.40(m, 1H), 6.40(m, 1H), 4.20-3.78(m, yl]pyrimidin-2-yl}-5- 5H), 3.20(m, 2H), 2.71(m, 2H), 2.62(m, 1H), 2.31(m, (trifluoromethyl)benzene- 1H), 1.75(m, 2H), 1.46(m, 2H), 1.37(m, 3H), 0.99(m, 3H) 1,3-diamine dihydrochloride 467 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.01-7.89(m, 1H), 7.59(m, (ethylamino)pyrrolidin-1- 1H), 7.20(t, 1H), 6.28(d, 1H), 4.08-3.75(m, 5H), 3.21- yl]pyrimidin-2-yl}-3- 3.11(m, 2H), 2.69(m, 2H), 2.58-2.52(m, 1H), 2.38- (trifluoromethyl)benzene- 2.27(m, 1H), 1.73(m, 2H), 1.45(m, 2H), 1.37(m, 3H), 1,4-diamine dihydrochloride 1.00(m, 3H) 468 (S)-4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16-8.10(m, 1H), 7.78(m, (ethylamino)pyrrolidin-1-yl]- 1H), 7.41(m, 1H), 6.33(s, 1H), 4.07-3.76(m, 5H), 3.21- N-[4-fluoro-3- 3.19(m, 2H), 2.73(m, 2H), 2.56(m, 1H), 2.28(m, 1H), (trifluoromethyl)phenyl]pyrim- 1.72(m, 2H), 1.44(m, 2H), 1.36(m, 3H), 1.00(m, 3H) idin-2-amine dihydrochloride 469 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.14(m, 1H), 7.87(m, 1H), (ethylamino)pyrrolidin-1- 7.44(m, 1H), 6.34(s, 1H), 4.08(m, 2H), 3.90-3.76(m, 3H), yl]pyrimidin-2-ylamino}-2- 3.19(m, 2H), 2.71(m, 2H), 2.59(m, 1H), 2.30(m, 1H), fluorobenzonitrile 1.74(m, 2H), 1.48(m, 2H), 1.37(m, 3H), 1.00(m, 3H) dihydrochloride 470 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.78-7.72(m, 1H), 7.45(m, (ethylamino)pyrrolidin-1- 1H), 7.35-7.32(m, 1H), 6.31(s, 1H), 4.12-3.76(m, 5H), yl]pyrimidin-2-yl}-4- 3.20(m, 2H), 2.72(m, 2H), 2.52(m, 1H), 2.30(m, 1H), fluorobenzene-1,3-diamine 1.74(m, 2H), 1.39(m, 2H), 1.37(m, 3H), 1.00(m, 3H) dihydrochloride 471 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.62(m, 1H), 7.47(m, 1H), (ethylamino)pyrrolidin-1- 7.33(m, 1H), 6.30(s, 1H), 4.17-3.76(m, 5H), 3.20(m, 2H), yl]pyrimidin-2-yl}-4- 2.70(m, 2H), 2.40(m, 1H), 2.30(m, 1H), 1.74(m, 2H), chlorobenzene-1,3-diamine 1.47(m, 2H), 1.39(m, 3H), 1.00(m, 3H) dihydrochloride 472 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 9.25(brs, NH), 8.27(s, 1H), methylphenylamino)-6- 7.51(d, 1H), 7.16(d, 1H), 6.94(brs, NH), 5.67(s, 1H), propylpyrimidin-4- 4.66(m, 1H), 4.14(s, 2H), 3.81-3.44(m, 4H), 2.47(m, 5H), yl]pyrrolidin-3-yl}-2- 2.33(m, 1H), 2.10(m, 1H), 1.68(m, 2H), 0.98(t, 3H) hydroxyacetamide

TABLE 1-49 Example Compound NMR Spectrum 473 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(s, 1H), 7.58(d, 1H), fluorophenylamino)-6- 7.10(m, 1H), 6.76(brs, NH), 5.74(s, 1H), 4.67(m, 1H), propylpyrimidin-4- 4.14(s, 2H), 3.81-3.42(m, 4H), 2.47(t, 2H), 2.34(m, 1H), yl]pyrrolidin-3-yl}-2- 2.04(m, 1H), 1.72(m, 2H), 0.98(t, 3H) hydroxyacetamide 474 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CDCl₃) δ 7.56(s, NH), 7.10-7.02(m, cyanophenylamino)-6- 2H), 6.69(m, 1H), 6.51(s, 1H), 5.73(s, 1H), 4.64(m, 1H), propylpyrimidin-4- 4.14(s, 2H), 3.85(brs, 2NH), 3.81-3.49(m, 4H), 2.49(t, yl]pyrrolidin-3-yl}-2- 2H), 2.35(m, 1H), 2.06(m, 1H), 1.72(m, 2H), 0.98(t, 3H) hydroxyacetamide 475 (S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CDCl₃) δ 7.63(s, NH), 7.10-6.98(m, (trifluoromethyl)phenylamino]- 2H), 6.78(m, 1H), 6.51(s, 1H), 5.68(s, 1H), 4.64(m, 1H), 6-propylpyrimidin-4- 4.13(s, 2H), 3.83(brs, 2NH), 3.49(m, 4H), 2.45(t, 2H), yl}pyrrolidin-3-yl)-2- 2.30(m, 1H), 2.04(m, 1H), 1.68(m, 2H), 0.96(t, 3H) hydroxyacetamide 476 (S)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.11(brs, NH), 7.26(m, 2H), (trifluoromethyl)phenylamino]- 6.94(brs, NH), 6.68(m, 1H), 5.63(s, 1H), 4.66(m, 1H), 6-propylpyrimidin-4- 4.15(s, 2H), 4.00(brs, 2NH), 3.76-3.63(m, 4H), 2.43(t, yl}pyrrolidin-3-yl)-2- 2H), 2.31(m, 1H), 2.08(m, 1H), 1.70(m, 2H), 0.96(t, 3H) hydroxyacetamide 477 (S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, NH), 7.45(m, 1H), (trifluoromethyl)phenylamino]- 7.08(m, 2H), 6.70(m, 1H), 5.72(s, 1H), 4.66(m, 1H), 6-propylpyrimidin-4- 4.15(s, 2H), 3.78-3.41(m, 4H), 2.46(t, 2H), 2.34(m, 1H), yl}pyrrolidin-3-yl)-2- 2.04(m, 1H), 1.70(m, 2H), 0.97(t, 3H) hydroxyacetamide 478 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.21(m, 1H), 6.86(m, 2H), fluorophenylamino)-6- 6.80(brs, NH), 5.64(s, 1H), 4.64(m, 1H), 4.15(s, 2H), propylpyrimidin-4- 3.76(brs, 2NH), 3.63-3.59(m, 4H), 2.44(t, 2H), 2.31(m, yl]pyrrolidin-3-yl}-2- 1H), 2.05(m, 1H), 1.70(m, 2H), 0.97(t, 3H) hydroxyacetamide 479 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.25(s, 1H), 7.06(m, 1H), chlorophenylamino)-6- 6.92(m, 1H), 5.89(s, 1H), 4.55(m, 1H), 3.99(s, 2H), 3.87- propylpyrimidin-4- 3.62(m, 4H), 2.49(t, 2H), 2.31(m, 1H), 2.10(m, 1H), yl]pyrrolidin-3-yl}-2- 1.71(m, 2H), 0.99(t, 3H) hydroxyacetamide 480 (S)-N-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.96(brs, NH), 7.21(m, 1H), methylphenylamino)-6- 7.09(m, 1H), 6.92(brs, NH), 6.76(m, 1H), 5.67(s, 1H), propylpyrimidin-4- 4.67(m, 1H), 4.14(s, 2H), 3.77-3.43(m, 4H), 2.45(t, 2H), yl]pyrrolidin-3-yl}-2- 2.31(m, 4H), 2.04(m, 1H), 1.69(m, 2H), 0.97(t, 3H) hydroxyacetamide 481 (S)-2-hydroxy-N-(1-{2-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, NH), 7.38(m, 1H), methyl-3- 7.16(m, 2H), 6.78(m, 1H), 5.67(s, 1H), 4.66(m, 1H), (trifluoromethyl)phenylamino]- 4.14(s, 2H), 3.76-3.61(m, 4H), 2.47(m, 5H), 2.30(m, 1H), 6-propylpyrimidin-4- 2.04(m, 1H), 1.70(m, 2H), 0.96(t, 3H) yl}pyrrolidin-3-yl)acetamide

TABLE 1-50 Example Compound NMR Spectrum 482 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 7.73(m, 2H), 7.22(d, 1H), cyanophenylamino)-6- 6.31(d, 1H), 4.57(m, 1H), 4.05(s, 2H), 3.95-3.54(m, 4H), propylpyrimidin-4- 2.67(m, 2H), 2.38(m, 1H), 2.19(m, 2H), 1.80(m, 2H), yl]pyrrolidin-3-yl}-2- 1.05(m, 3H) hydroxyacetamide hydrochloride 483 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.02(d, 1H), 7.71(m, 1H), methylphenylamino)-6- 7.43(d, 1H), 6.27(d, 1H), 4.56(m, 1H), 3.99(s, 2H), 3.90- propylpyrimidin-4- 3.47(m, 4H), 2.64(m, 2H), 2.52(s, 3H), 2.17(m, 1H), yl]pyrrolidin-3-yl}-2- 2.01(m, 1H), 1.78(m, 2H), 1.05(m, 3H) hydroxyacetamide hydrochloride 484 (S)-4-fluoro-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.67-7.62(m, 1H), 7.44- (methylamino)pyrrolidin-1- 7.28(m, 2H), 6.30(d, 1H), 4.12-3.76(m, 5H), 2.81(d, 3H), yl]-6-propylpyrimidin-2- 2.67(dd, 2H), 2.60-2.01(m, 2H), 1.82-1.62(m, 2H), 1.05(t, yl}benzene-1,3-diamine 3H) dihydrochloride 485 (S)-3-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.79(d, 1H), 7.67(d, 1H), (methylamino)pyrrolidin-1- 7.21(s, 1H), 6.36(d, 1H), 4.19-3.77(m, 5H), 2.82(d, 3H), yl]-6-propylpyrimidin-2- 2.70(dd, 2H), 2.64-2.36(m, 2H), 1.84-1.77(m, 2H), 1.05(t, yl}amino)benzonitrile 3H) dihydrochloride 486 (S)-2-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.63-7.62(m, 1H), 7.43- (methylamino)pyrrolidin-1- 7.39(m, 1H), 6.90(d, 1H), 6.24(d, 1H), 4.12-3.73(m, 5H), yl]-6-propylpyrimidin-2- 2.79(d, 3H), 2.64(dd, 2H), 2.59-2.25(m, 2H), 1.79- yl}amino)benzonitrile 1.73(m, 2H), 1.04(t, 3H) dihydrochloride 487 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.74(d, 1H), 7.47(d, 1H), (methylamino)pyrrolidin-1- 7.10(s, 1H), 6.35(s, 1H), 4.20-3.70(m, 5H), 2.81(d, 3H), yl]-6-propylpyrimidin-2-yl}-5- 2.69(t, 2H), 2.69-2.50(m, 1H), 2.45-2.25(m, 1H), 1.90- (trifluoromethyl)benzene- 1.70(m, 2H), 1.06(t, 3H) 1,3-diamine dihydrochloride 488 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.79(d, 1H), 7.50-7.40(m, (ethylamino)pyrrolidin-1-yl]- 1H), 7.02(t, 1H), 6.30-6.20(m, 1H), 4.20-3.60(m, 5H), 6-propylpyrimidin-2-yl}-3- 3.25-3.00(m, 2H), 2.65(t, 2H), 2.60-2.40(m, 1H), 2.40- (trifluoromethyl)benzene- 2.20(m, 1H), 1.78(q, 2H), 1.40-1.30(m, 3H), 1.05(t, 3H) 1,4-diamine dihydrochloride 489 (S)-2-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.69(d, 1H), 7.55-7.45(m, (ethylamino)pyrrolidin-1-yl]- 1H), 6.96(d, 1H), 6.25(d, 1H), 4.15-3.60(m, 5H), 3.25- 6-propylpyrimidin-2- 3.05(m, 2H), 2.65(t, 2H), 2.65-2.45(m, 1H), 2.40-2.20(m, yl}amino)benzonitrile 1H), 1.75(q, 2H), 1.37(t, 3H), 1.04(t, 3H) dihydrochloride 490 (S)-N-[4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.47(d, 1H), 7.75-7.65(m, (trifluoromethyl)phenyl]-4- 1H), 7.20(t, 1H), 5.97(s, 1H), 4.00-3.85(m, 2H), 3.85- [3-(methylamino)pyrrolidin- 3.50(m, 3H), 2.78(s, 3H), 2.60-2.40(m, 3H), 2.30-2.20(m, 1-yl]-6-propylpyrimidin-2- 1H), 1.74(q, 2H), 0.98(t, 3H) amine hydrochloride

TABLE 1-51 Example Compound NMR Spectrum 491 (S)-4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.45(d, 1H), 7.71(d, 1H), (ethylamino)pyrrolidin-1-yl]- 7.20(t, 1H), 5.97(s, 1H), 4.10-3.85(m, 2H), 3.85-3.50(m, N-[4-fluoro-3- 3H), 3.16(t, 2H), 2.60-2.40(m, 3H), 2.30-2.15(m, 1H), (trifluoromethyl)phenyl]-6- 1.75(q, 2H), 1.36(t, 3H), 0.98(t, 3H) propylpyrimidin-2-amine hydrochloride 492 (S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.97(d, 1H), 7.71(t, 1H), cyano-4- 7.44(d, 1H), 6.24(d, 1H), 4.48(d, 1H), 4.00-3.40(m, 4H), methylphenylamino)pyrimidin- 2.67(t, 2H), 2.52(s, 3H), 2.40-2.20(m, 1H), 2.15-2.00(m, 4-yl]pyrrolidin-3- 1H), 1.95(s, 3H), 1.80-1.60(m, 2H), 1.45(q, 2H), 0.98(t, yl}acetamide hydrochloride 3H) 493 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.00(d, 1H), 6.92(s, 1H), methylphenylamino)-6- 6.76(t, 1H), 6.14(d, 1H), 4.47(d, 1H), 4.00-3.35(m, 4H), propylpyrimidin-4- 2.60(t, 2H), 2.40-2.20(m, 1H), 2.13(s, 3H), 2.15-2.00(m, yl]pyrrolidin-3-yl}acetamide 1H), 1.95(s, 3H), 1.74(q, 2H), 1.03(t, 3H) hydrochloride 494 (S)-N-(1-{2-[(3,4- ¹H-NMR(400 MHz, CD₃OD) δ 6.88(s, 1H), 6.70(m, 2H), diaminophenyl)amino]-6- 6.02(s, 1H), 4.45(brs, 1H), 3.83-3.63(m, 3H), 2.55(m, propylpyrimidin-4- 2H), 2.28(br, 1H), 2.03(br, 1H), 1.97(s, 3H), 1.72(m, 2H), yl}pyrrolidin-3-yl)acetamide 1.01(t, 3H)

Test Example 1: Evaluation of Agonistic Activity in CHO-K1 Cells Expressing Human 5-HT_(4(a))

As CHO-K1 cells stably expressing human 5-HT_(4(a)), we used the GeneBIAzer HTR4-CRE-bla CHO-K1 cells (Invitrogen Corp.). The cells were cultured, under the condition of 37

and 5% CO₂, in a DMEM supplemented with 10% fetal bovine serum (FBS), 25 mM HEPES (pH7.4), 600 μg/ml hygromycin B, 0.1 mM non-essential amino acids, 100 unit/ml penicillin and 100 μg/ml streptomycin. Subcultures were performed three times per one week, each being at less than 80% confluence. At the previous day before treating test compounds, the cells were collected using 0.5% trypsin/EDTA and then diluted with a DMEM supplemented with 1% FBS, 25 mM HEPES, and 0.1 mM non-essential amino acids into 3.125×10⁵ cells/ml. 32 μl of the diluted cells were added into 384-well plate (10⁴ cells per well) and then incubated overnight. After the overnight culture, 8 μl of the medium having 1% of DMSO was added into the cell-free control well and the non-stimulating control well, respectively. 8 μl of the respective test compound dilutions (which had been prepared by diluting by 100-times with the medium as mentioned in the above) having 1% of DMSO were added to the respective remaining wells. After being cultured in the incubator for 5 hours, the wells of the 384-plate were treated with the substrate solution (8 μl per well) prepared according to the vendor's instruction (i.e., Invitrogen's instruction), and then incubated in the dark room for additional two hours. Agonistic activities on 5-HT₄ receptor were evaluated, on the basis of fluorescence values of the cleavage-products by beta-lactamase. After exciting to 410 nm of wavelength using a fluorescence detector (Genios Pro), we measured the fluorescence values at two emission wavelengths (first wavelength: 465 nm, second wavelength: 535 nm). Data were analyzed on the basis of the ratio of fluorescence intensities of each well at the respective wavelengths. Each EC₅₀ value was calculated by non-linear regression analysis using the “GraphPad Prism” program, based on the activities according to 8-different concentrations of the test compounds. The results are shown in Table 2-1 to 2-3 below.

TABLE 2-1 Example EC₅₀(nM) 13 0.12 17 0.35 18 0.14 22 0.33 31 0.13 32 0.23 33 0.059 34 0.16 36 0.243 40 0.03 41 0.15 42 0.033 43 0.178 44 0.022 45 0.036 46 0.0097 47 0.38 50 0.012 52 0.33 53 0.098 54 0.032 55 0.016 56 0.312 57 0.389 59 0.028 60 0.047 61 0.15 62 0.36 63 0.13 66 0.1 67 0.19 71 0.25 73 0.27 75 0.22 77 0.15 78 0.28 79 0.44 80 0.17 81 0.205 82 0.048 84 0.031 85 0.003 86 0.039 87 0.048 88 0.041 89 0.08 90 0.091 91 0.014 92 0.057 93 0.01 94 0.041 95 0.081 96 0.017 97 0.046 98 0.094 99 0.0015 100 0.31 102 0.39 103 0.067 104 0.073 105 0.005 106 0.13 107 0.42 108 0.21 109 0.012 110 0.018 111 0.008 112 0.045 113 0.016 116 0.0035 117 0.014 121 0.005 123 0.0019 125 0.159 127 0.0062 128 0.039 129 0.323 131 0.091 133 0.039 134 0.214 135 0.011 136 0.045 137 0.072 138 0.012 139 0.034 140 0.028 141 0.085 142 0.01 143 0.0066 144 0.036 145 0.046 146 0.084 149 0.277 150 0.41 151 0.334 153 0.228 155 0.417 156 0.219 157 0.044 158 0.436 160 0.121 161 0.119 162 0.193 165 0.2 166 0.103 170 0.0013 171 0.00064 173 0.004 175 0.229 176 0.018 177 0.02 180 0.0087 181 0.00088 182 0.036 185 0.015 186 0.382 187 0.037 189 0.028 190 0.05 191 0.29 192 0.02 194 0.2 195 0.25 196 0.1 203 0.3 204 0.47 206 0.16 207 0.083 208 0.06 210 0.016 211 0.019 212 0.0089 213 0.017 214 0.029 215 0.018 217 0.23 220 0.07 221 0.149 222 0.082 223 0.011 224 0.0043 225 0.052 226 0.052 228 0.014

TABLE 2-2 Example EC₅₀(nM) 229 0.00098 230 0.047 231 0.0067 232 0.13 233 0.019 234 0.0012 235 0.0023 236 0.209 237 0.0013 238 0.00039 239 0.115 240 0.0025 241 0.012 242 0.058 243 0.011 244 0.028 245 0.053 246 0.04 247 0.012 248 0.016 249 0.0018 251 0.01 252 0.0052 253 0.014 254 0.0015 255 0.023 260 0.015 261 0.0071 262 0.0039 268 0.011 270 0.204 274 0.087 279 0.078 280 0.026 281 0.196 282 0.103 286 0.0047 289 0.062 290 0.013 291 0.0074 292 0.038 293 0.0043 294 0.076 295 0.048 296 0.039 297 0.028 301 0.11 302 0.42 303 0.12 304 0.07 305 0.18 307 0.24 309 0.076 310 0.37 311 0.019 312 0.023 313 0.078 314 0.18 315 0.028 316 0.21 317 0.14 318 0.16 319 0.08 320 0.041 321 0.044 322 0.15 323 0.027 325 0.085 326 0.028 327 0.025 328 0.017 329 0.18 331 0.138 332 0.046 333 0.024 334 0.085 337 0.0026 338 0.0032 342 0.0055 344 0.0092 345 0.062 346 0.014 347 0.03 348 0.019 349 0.016 350 0.012 351 0.0035 352 0.0027 353 0.01 354 0.003 355 0.007 357 0.0065 358 0.014 359 0.0021 362 0.0021 364 0.122 365 0.027 366 0.078 367 0.153 368 0.182 369 0.049 370 0.015 372 0.0046 373 0.0043 374 0.0027 375 0.0033 376 0.0037 377 0.0013 378 0.015 379 0.0098 380 0.009 381 0.0043 382 0.0051 383 0.0057 384 0.077 387 0.007 395 0.082 399 0.13 400 0.033 401 0.073 402 0.236 403 0.414 405 0.399 406 0.402 407 0.254 414 0.0034 415 0.015 416 0.0074 417 0.0051 418 0.0022 419 0.0032 420 0.0029 421 0.0079 422 0.011 423 0.0084 424 0.02 425 0.056 426 0.079 427 0.024 428 0.066 429 0.025 430 0.027 431 0.029 433 0.055

TABLE 2-3 Example EC₅₀(nM) 434 0.111 436 0.01 437 0.02 438 0.015 439 0.0075 440 0.017 441 0.0095 442 0.041 443 0.0099 444 0.012 445 0.0098 446 0.0077 447 0.0023 448 0.0025 449 0.0044 450 0.0078 451 0.003 452 0.0033 453 0.0016 454 0.014 455 0.0038 456 0.0026 457 0.003 458 0.0017 459 0.0034 460 0.0019 461 0.0019 462 0.0026 463 0.0021 464 0.0039 465 0.0022 466 0.0058 467 0.0014 468 0.0062 469 0.0021 470 0.0025 471 0.0033 472 0.0075 473 0.022 474 0.0066 475 0.011 476 0.014 477 0.0096 478 0.024 479 0.0064 480 0.032 481 0.0093 484 0.0058 485 0.0024 486 0.0014 487 0.0021 488 0.00077 489 0.0015 490 0.0048 491 0.0029 492 0.019 493 0.024

As shown in Table 2-1 to 2-3, the compounds of the present invention have excellent activities as a 5-HT₄ receptor agonist, and therefore they can be usefully applied for preventing or treating the dysfunction in gastrointestinal motility. 

The invention claimed is:
 1. A compound of Formula 1 or its pharmaceutically acceptable salt:

wherein, R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl, dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkyl group, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.
 2. The compound or its pharmaceutically acceptable salt of claim 1, wherein R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E, R₄ is hydrogen, R₅ is a C₁₋₅ alkyl group, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.
 3. A pharmaceutical composition for agonizing a 5-HT₄ receptor, comprising a therapeutically effective amount of a compound of Formula 1 or its pharmaceutically acceptable salt; and a pharmaceutically acceptable carrier:

wherein, R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl, dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkyl group, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group, wherein the agonizing a 5-HT₄ receptor effects to treat a dysfunction in gastrointestinal motility in a disease selected from the group consisting of gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, and diabetic gastric atony.
 4. The pharmaceutical composition of claim 3, wherein R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E, R₄ is hydrogen, R₅ is a C₁₋₅ alkyl group, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.
 5. A method of agonizing a 5-HT₄ receptor and treating a dysfunction in gastrointestinal motility in a disease selected from the group consisting of gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, and diabetic gastric atony, comprising administering an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof:

wherein, R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino, C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl, quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl, dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl, benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of amino, di-C₁₋₅ alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or an oxo (═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the following Formulas A to E (where * in Formulas A to E represents the position attached to the compounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionally substituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆ alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkyl group, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group, wherein the administrating of the compound or the pharmaceutical salt thereof agonizes a 5 HT₄ receptor and treats the dysfunction in the subject.
 6. The method of claim 5, wherein R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein the heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen) and acetyl, R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where the benzylamino is optionally substituted with halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a group selected from the group consisting of the Formulas A, B, D and E, R₄ is hydrogen, R₅ is a C₁₋₅ alkyl group, R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl (where the piperazinyl is optionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionally substituted with phenyl; a trifluoromethyl group; a trifluoroethyl group; or a phenyl group optionally substituted with halogen, R₇ is hydrogen, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituent selected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where the furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety is optionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group. 